6407 lines
700 KiB
Text
6407 lines
700 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- *606241 - DICER 1, RIBONUCLEASE III; DICER1
|
|
|
|
|
|
- OMIM
|
|
|
|
</title>
|
|
|
|
|
|
|
|
</head>
|
|
|
|
<body>
|
|
<div id="mimBody">
|
|
|
|
|
|
|
|
<div id="mimHeader" class="hidden-print">
|
|
|
|
|
|
|
|
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
|
|
<div class="container-fluid">
|
|
|
|
<!-- Brand and toggle get grouped for better mobile display -->
|
|
<div class="navbar-header">
|
|
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
|
|
<span class="sr-only"> Toggle navigation </span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
</button>
|
|
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
|
|
</div>
|
|
|
|
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
|
|
|
|
<ul class="nav navbar-nav">
|
|
|
|
|
|
<li>
|
|
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
|
|
<li>
|
|
<a href="/statistics/update"> Update List </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/entry"> Entry Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
|
|
|
|
<li>
|
|
<a href="/downloads/"> Register for Downloads </a>
|
|
</li>
|
|
<li>
|
|
<a href="/api"> Register for API Access </a>
|
|
</li>
|
|
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="/contact?mimNumber=606241"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
<span class="hidden-sm hidden-xs">
|
|
|
|
|
|
Display:
|
|
|
|
|
|
<label style="font-weight: normal"><input type="checkbox" id="mimToggleChangeBars" checked /> Change Bars </label>
|
|
|
|
|
|
</span>
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">*606241</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#cloning">Cloning and Expression</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#biochemicalFeatures">Biochemical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#geneFunction">Gene Function</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
|
|
</li>
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="/allelicVariants/606241">Table View</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000100697;t=ENST00000343455" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=23405" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=606241" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000100697;t=ENST00000343455" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001195573,NM_001271282,NM_001291628,NM_001395677,NM_001395678,NM_001395679,NM_001395680,NM_001395682,NM_001395683,NM_001395684,NM_001395685,NM_001395686,NM_001395687,NM_001395688,NM_001395689,NM_001395690,NM_001395691,NM_001395692,NM_001395693,NM_001395694,NM_001395695,NM_001395696,NM_001395697,NM_001395698,NM_001395699,NM_001395700,NM_030621,NM_177438,NR_172715,NR_172716,NR_172717,NR_172718,NR_172719,NR_172720" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_177438" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=606241" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://hprd.org/summary?hprd_id=05875&isoform_id=05875_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.proteinatlas.org/search/DICER1" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/protein/5019620,6102924,20521696,21665773,29294649,29294651,56967456,56967458,60280988,60280990,60280992,119602001,119602002,152012889,193786026,193787170,257051056,298217471,300517087,300599719,307133775,404312696,618468591,673163841,2069681546,2074816056,2074816069,2074816090,2074816096,2074816191,2074816194,2074816207,2074816236,2074816256,2074816259,2074816265,2074816282,2074816284,2074816287,2074816289,2074816291,2074816293,2074816297,2074816299,2074816301,2074816303,2074816305,2075472757,2436992063" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.uniprot.org/uniprotkb/Q9UPY3" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Gene Info</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="http://biogps.org/#goto=genereport&id=23405" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000100697;t=ENST00000343455" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=DICER1" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=DICER1" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+23405" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
<dd><a href="http://v1.marrvel.org/search/gene/DICER1" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
|
|
|
|
|
|
|
|
<dd><a href="https://monarchinitiative.org/NCBIGene:23405" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/23405" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr14&hgg_gene=ENST00000343455.8&hgg_start=95086228&hgg_end=95158010&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:17098" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:17098" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://medlineplus.gov/genetics/gene/dicer1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606241[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606241[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.deciphergenomics.org/gene/DICER1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000100697" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.ebi.ac.uk/gwas/search?query=DICER1" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
|
|
|
|
|
|
|
|
<div><a href="https://www.gwascentral.org/search?q=DICER1" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=DICER1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=DICER1&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.pharmgkb.org/gene/PA38437" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/gene/HGNC:17098" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://flybase.org/reports/FBgn0039016.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mousephenotype.org/data/genes/MGI:2177178" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://v1.marrvel.org/search/gene/DICER1#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/marker/MGI:2177178" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gene/23405/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orthodb.org/?ncbi=23405" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00000939;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://zfin.org/ZDB-GENE-030131-3445" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cellular Pathways</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:23405" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://reactome.org/content/query?q=DICER1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 702411003, 782722002<br />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
606241
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
DICER 1, RIBONUCLEASE III; DICER1
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
DICER, DROSOPHILA, HOMOLOG OF, 1<br />
|
|
DCR1<br />
|
|
HELICASE WITH RNASE MOTIF; HERNA<br />
|
|
HELICASE-MOI<br />
|
|
K12H4.8-LIKE<br />
|
|
KIAA0928
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=DICER1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">DICER1</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/14/500?start=-3&limit=10&highlight=500">14q32.13</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:95086228-95158010&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">14:95,086,228-95,158,010</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=618272,138800,601200,180295" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/14/500?start=-3&limit=10&highlight=500">
|
|
14q32.13
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
GLOW syndrome, somatic mosaic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/618272"> 618272 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/138800"> 138800 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Pleuropulmonary blastoma
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601200"> 601200 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Rhabdomyosarcoma, embryonal, 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/180295"> 180295 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/606241" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/606241" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The DICER1 gene, a member of the ribonuclease III (RNaseIII) family, is involved in the generation of microRNAs (miRNAs), which modulate gene expression at the posttranscriptional level (summary by <a href="#52" class="mim-tip-reference" title="Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others. <strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong> J.A.M.A. 305: 68-77, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205968">Rio Frio et al., 2011</a>). DICER1 possesses an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus DICER, also known as helicase-MOI, is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression (<a href="#37" class="mim-tip-reference" title="Matsuda, S., Ichigotani, Y., Okuda, T., Irimura, T., Nakatsugawa, S., Hamaguchi, M. <strong>Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.</strong> Biochim. Biophys. Acta 1490: 163-169, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10786632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10786632</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00221-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10786632">Matsuda et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21205968+10786632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Evidence also suggests that DICER1 may act as a haploinsufficient tumor suppressor gene (<a href="#1" class="mim-tip-reference" title="Bahubeshi, A., Bal, N., Rio Frio, T., Hamel, N., Pouchet, C., Yilmaz, A., Bouron-Dal Soglio, D., Williams, G. M., Tischkowitz, M., Priest, J. R., Foulkes, W. D. <strong>Germline DICER1 mutations and familial cystic nephroma.</strong> J. Med. Genet. 47: 863-866, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21036787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21036787</a>] [<a href="https://doi.org/10.1136/jmg.2010.081216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21036787">Bahubeshi et al., 2010</a>; <a href="#52" class="mim-tip-reference" title="Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others. <strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong> J.A.M.A. 305: 68-77, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205968">Rio Frio et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21205968+21036787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="cloning" class="mim-anchor"></a>
|
|
<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimCloningFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>To identify proteins interacting with 5-lipoxygenase (ALOX5; <a href="/entry/152390">152390</a>), <a href="#49" class="mim-tip-reference" title="Provost, P., Samuelsson, B., Radmark, O. <strong>Interaction of 5-lipoxygenase with cellular proteins.</strong> Proc. Nat. Acad. Sci. 96: 1881-1885, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051563</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051563[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.5.1881" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10051563">Provost et al. (1999)</a> used a yeast 2-hybrid approach to screen a human lung cDNA library. A 2.1-kb clone contained a partial cDNA of a human protein with high homology to the hypothetical helicase K12H4.8 from C. elegans. Analysis of the predicted amino acid sequence revealed the presence of an RNase III motif and a double-stranded RNA (dsRNA)-binding domain, indicative of a protein of nuclear origin. C. elegans K12H4.8 and the human homolog share 58% identity over 275 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Matsuda, S., Ichigotani, Y., Okuda, T., Irimura, T., Nakatsugawa, S., Hamaguchi, M. <strong>Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.</strong> Biochim. Biophys. Acta 1490: 163-169, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10786632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10786632</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00221-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10786632">Matsuda et al. (2000)</a> isolated a full-length cDNA encoding a gene they called HERNA for 'helicase with RNase motif.' The HERNA cDNA consists of 7,037 basepairs and has a predicted open reading frame encoding 1,924 amino acids. <a href="#37" class="mim-tip-reference" title="Matsuda, S., Ichigotani, Y., Okuda, T., Irimura, T., Nakatsugawa, S., Hamaguchi, M. <strong>Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.</strong> Biochim. Biophys. Acta 1490: 163-169, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10786632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10786632</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00221-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10786632">Matsuda et al. (2000)</a> also recognized the homology to C. elegans K12H4.8. HERNA expression was detected by cycle-limited RT-PCR in brain, heart, lung, liver, pancreas, kidney, and placenta, but not in skeletal muscle, suggesting that HERNA may be ubiquitously expressed at variable levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10786632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#37" class="mim-tip-reference" title="Matsuda, S., Ichigotani, Y., Okuda, T., Irimura, T., Nakatsugawa, S., Hamaguchi, M. <strong>Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.</strong> Biochim. Biophys. Acta 1490: 163-169, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10786632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10786632</a>] [<a href="https://doi.org/10.1016/s0167-4781(99)00221-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10786632">Matsuda et al. (2000)</a> used PCR-based monochromosomal somatic cell hybrid mapping to localize the HERNA gene to human chromosome 14. Analysis of radiation hybrid mapping panels refined the localization to 14q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10786632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="biochemicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimBiochemicalFeaturesFold" id="mimBiochemicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimBiochemicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimBiochemicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
<a href="#34" class="mim-tip-reference" title="MacRae, I. J., Zhou, K., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., Adams, P. D., Doudna, J. A. <strong>Structural basis for double-stranded RNA processing by Dicer.</strong> Science 311: 195-198, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16410517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16410517</a>] [<a href="https://doi.org/10.1126/science.1121638" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16410517">MacRae et al. (2006)</a> determined the crystal structure of DICER. In an intact DICER enzyme, the PAZ domain, a module that binds the end of dsRNA, is separated from the 2 catalytic RNase III domains by a flat, positively charged surface. The 65-angstrom distance between the PAZ and RNase III domains matches the length spanned by 25 basepairs of RNA. Thus, <a href="#34" class="mim-tip-reference" title="MacRae, I. J., Zhou, K., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., Adams, P. D., Doudna, J. A. <strong>Structural basis for double-stranded RNA processing by Dicer.</strong> Science 311: 195-198, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16410517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16410517</a>] [<a href="https://doi.org/10.1126/science.1121638" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16410517">MacRae et al. (2006)</a> concluded that Dicer itself is a molecular ruler that recognizes dsRNA and cleaves a specified distance from the helical end. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16410517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="geneFunction" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>The 21-nucleotide small temporal RNA (stRNA) let7 (<a href="/entry/605386">605386</a>) regulates developmental timing in C. elegans and probably in other bilateral animals. <a href="#25" class="mim-tip-reference" title="Hutvagner, G., McLachlan, J., Pasquinelli, A. E., Balint, E., Tuschl, T., Zamore, P. D. <strong>A cellular function for the RNA-interference enzyme dicer in the maturation of the let-7 small temporal RNA.</strong> Science 293: 834-838, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452083</a>] [<a href="https://doi.org/10.1126/science.1062961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11452083">Hutvagner et al. (2001)</a> presented in vivo and in vitro evidence that in Drosophila, a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let7 stRNA. Targeted disruption in cultured human cells of the mRNA encoding the enzyme DICER, which acts in the RNA interference pathway, leads to accumulation of the LET7 precursor. Thus, <a href="#25" class="mim-tip-reference" title="Hutvagner, G., McLachlan, J., Pasquinelli, A. E., Balint, E., Tuschl, T., Zamore, P. D. <strong>A cellular function for the RNA-interference enzyme dicer in the maturation of the let-7 small temporal RNA.</strong> Science 293: 834-838, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452083</a>] [<a href="https://doi.org/10.1126/science.1062961" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11452083">Hutvagner et al. (2001)</a> concluded that the RNA interference and stRNA pathways intersect. Both pathways require the RNA processing enzyme DICER to produce the active small RNA component that represses gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11452083" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In S. pombe, <a href="#58" class="mim-tip-reference" title="Volpe, T. A., Kidner, C., Hall, I. M., Teng, G., Grewal, S. I. S., Martienssen, R. A. <strong>Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi.</strong> Science 297: 1833-1837, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12193640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12193640</a>] [<a href="https://doi.org/10.1126/science.1074973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12193640">Volpe et al. (2002)</a> deleted the argonaute (AGO1, or EIF2C1; <a href="/entry/606228">606228</a>), DICER, and RNA-dependent RNA polymerase gene homologs, which encode part of the machinery responsible for RNA interference. Deletion resulted in the aberrant accumulation of complementary transcripts from centromeric heterochromatic repeats. This was accompanied by transcription of derepression of transgenes integrated at the centromere, loss of histone H3 (see <a href="/entry/602810">602810</a>) lysine-9 methylation, and impairment of centromere function. <a href="#58" class="mim-tip-reference" title="Volpe, T. A., Kidner, C., Hall, I. M., Teng, G., Grewal, S. I. S., Martienssen, R. A. <strong>Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi.</strong> Science 297: 1833-1837, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12193640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12193640</a>] [<a href="https://doi.org/10.1126/science.1074973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12193640">Volpe et al. (2002)</a> proposed that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNA interference. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12193640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>DICER contains 2 domains related to the bacterial double-stranded RNA (dsRNA)-specific endonuclease, RNase III, which functions as a homodimer. Based on an x-ray structure of the Aquifex aeolicus RNase III, <a href="#4" class="mim-tip-reference" title="Blaszczyk, J., Tropea, J. E., Bubunenenko, M., Routzahn, K. M., Waugh, D. S., Court, D. L., Ji, X. <strong>Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage.</strong> Structure 9: 1225-1236, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11738048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11738048</a>] [<a href="https://doi.org/10.1016/s0969-2126(01)00685-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11738048">Blaszczyk et al. (2001)</a> proposed models of the enzyme interaction with dsRNA and its cleavage at 2 composite catalytic centers. <a href="#63" class="mim-tip-reference" title="Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E., Filipowicz, W. <strong>Single processing center models for human Dicer and bacterial RNase III.</strong> Cell 118: 57-68, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15242644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15242644</a>] [<a href="https://doi.org/10.1016/j.cell.2004.06.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15242644">Zhang et al. (2004)</a> generated mutations in human DICER and E. coli RNase III residues implicated in the catalysis and studied their effects on RNA processing. They determined that both enzymes have only 1 processing center that contains 2 RNA cleavage sites and generates products with 2-nucleotide 3-prime overhangs. <a href="#63" class="mim-tip-reference" title="Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E., Filipowicz, W. <strong>Single processing center models for human Dicer and bacterial RNase III.</strong> Cell 118: 57-68, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15242644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15242644</a>] [<a href="https://doi.org/10.1016/j.cell.2004.06.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15242644">Zhang et al. (2004)</a> proposed that DICER functions through intramolecular dimerization of its 2 RNase III domains, assisted by the flanking RNA-binding domains, PAZ and dsRBD. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11738048+15242644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#57" class="mim-tip-reference" title="Tomari, Y., Matranga, C., Haley, B., Martinez, N., Zamore, P. D. <strong>A protein sensor for siRNA asymmetry.</strong> Science 306: 1377-1380, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15550672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15550672</a>] [<a href="https://doi.org/10.1126/science.1102755" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15550672">Tomari et al. (2004)</a> showed that in Drosophila, the orientation of the DICER2/R2D2 protein heterodimer on the small interfering RNA (siRNA) duplex determines which siRNA strand associates with the core RNA-induced silencing complex (RISC) protein Argonaute-2 (AGO2, or EIF2C2; <a href="/entry/606229">606229</a>). R2D2 binds the siRNA end with the greatest double-stranded character, thereby orienting the heterodimer on the siRNA duplex. Strong R2D2 binding requires a 5-prime-phosphate on the siRNA strand that is excluded from the RISC. Thus, <a href="#57" class="mim-tip-reference" title="Tomari, Y., Matranga, C., Haley, B., Martinez, N., Zamore, P. D. <strong>A protein sensor for siRNA asymmetry.</strong> Science 306: 1377-1380, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15550672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15550672</a>] [<a href="https://doi.org/10.1126/science.1102755" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15550672">Tomari et al. (2004)</a> concluded that R2D2 is both a protein sensor for siRNA thermodynamic asymmetry and a licensing factor for entry of authentic siRNAs into the RNAi pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15550672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>AU-rich elements (AREs) in the 3-prime UTRs of unstable mRNAs dictate their degradation. Using an RNA interference-based screen in Drosophila S2 cells, <a href="#26" class="mim-tip-reference" title="Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.-C., Gram, H., Han, J. <strong>Involvement of microRNA in AU-rich element-mediated mRNA instability.</strong> Cell 120: 623-634, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15766526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15766526</a>] [<a href="https://doi.org/10.1016/j.cell.2004.12.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15766526">Jing et al. (2005)</a> found that Dicer-1, Ago1, and Ago2, components involved in microRNA (miRNA) processing and function, were required for rapid decay of mRNA containing AREs of tumor necrosis factor-alpha (TNF; <a href="/entry/191160">191160</a>). The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. <a href="#26" class="mim-tip-reference" title="Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.-C., Gram, H., Han, J. <strong>Involvement of microRNA in AU-rich element-mediated mRNA instability.</strong> Cell 120: 623-634, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15766526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15766526</a>] [<a href="https://doi.org/10.1016/j.cell.2004.12.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15766526">Jing et al. (2005)</a> showed that miRNA16 (miR16), a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, was required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay was sequence-specific and required the ARE-binding protein tristetraprolin (TTP, or ZFP36; <a href="/entry/190700">190700</a>). TTP did not directly bind miR16, but interacted through association with Ago/EIF2C family members to complex with miR16 and assist in the targeting of ARE. <a href="#26" class="mim-tip-reference" title="Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.-C., Gram, H., Han, J. <strong>Involvement of microRNA in AU-rich element-mediated mRNA instability.</strong> Cell 120: 623-634, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15766526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15766526</a>] [<a href="https://doi.org/10.1016/j.cell.2004.12.038" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15766526">Jing et al. (2005)</a> concluded that miRNA targeting of ARE appears to be an essential step in ARE-mediated mRNA degradation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15766526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R. <strong>TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. (Letter)</strong> Nature 436: 740-744, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15973356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15973356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15973356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature03868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15973356">Chendrimada et al. (2005)</a> demonstrated that TRBP (<a href="/entry/605053">605053</a>), which contains 3 double-stranded RNA-binding domains, is an integral component of a Dicer-containing complex. Biochemical analysis of TRBP-containing complexes revealed the association of Dicer-TRBP with AGO2, the catalytic engine of RISC. The physical association of Dicer-TRBP and AGO2 was confirmed after the isolation of the ternary complex using Flag-tagged AGO2 cell lines. In vitro reconstitution assays demonstrated that TRBP is required for the recruitment of AGO2 to the small interfering RNA (siRNA) bound by Dicer. Knockdown of TRBP resulted in destabilization of Dicer and a consequent loss of miRNA biogenesis. Finally, depletion of the Dicer-TRBP complex via exogenously introduced siRNAs diminished RISC-mediated reporter gene silencing. <a href="#7" class="mim-tip-reference" title="Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R. <strong>TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. (Letter)</strong> Nature 436: 740-744, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15973356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15973356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15973356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature03868" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15973356">Chendrimada et al. (2005)</a> concluded that these results support a role of the Dicer-TRBP complex not only in miRNA processing but also as a platform for RISC assembly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15973356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Hatfield, S. D., Shcherbata, H. R., Fischer, K. A., Nakahara, K., Carthew, R. W., Ruohola-Baker, H. <strong>Stem cell division is regulated by the microRNA pathway. (Letter)</strong> Nature 435: 974-978, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944714</a>] [<a href="https://doi.org/10.1038/nature03816" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944714">Hatfield et al. (2005)</a> reported the necessity of the miRNA pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell markers and genetic interactions, <a href="#22" class="mim-tip-reference" title="Hatfield, S. D., Shcherbata, H. R., Fischer, K. A., Nakahara, K., Carthew, R. W., Ruohola-Baker, H. <strong>Stem cell division is regulated by the microRNA pathway. (Letter)</strong> Nature 435: 974-978, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944714</a>] [<a href="https://doi.org/10.1038/nature03816" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944714">Hatfield et al. (2005)</a> concluded that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Maniataki, E., Mourelatos, Z. <strong>A human, ATP-independent, RISC assembly machine fueled by pre-miRNA.</strong> Genes Dev. 19: 2979-2990, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16357216[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1384005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16357216">Maniataki and Mourelatos (2005)</a> found that pre-miRNA-fueled assembly of RISC in humans differed from the assembly of RISC by siRNA in Drosophila in terms of the sequence of events, energy requirements, and the final RISC product. In human cells, DICER was associated with AGO2 prior to its encounter with pre-miRNA. The preformed AGO2/DICER-containing complex assembled RISCs from pre-miRNAs but not from siRNA duplexes, and the process was independent of added ATP or GTP. The final RISC product, a ribonucleoprotein made up of AGO2 and miRNA, could be released from DICER. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16357216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Gregory, R. I., Chendrimada, T. P., Cooch, N., Shiekhattar, R. <strong>Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.</strong> Cell 123: 631-640, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16271387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16271387</a>] [<a href="https://doi.org/10.1016/j.cell.2005.10.022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16271387">Gregory et al. (2005)</a> immunoprecipitated approximately 500-kD RISC complexes from human embryonic kidney cells and found that they contained DICER, TRBP, and AGO2. The RISC complex cleaved target RNA using pre-miRNA hairpin as well as duplex siRNA, but it displayed nearly 10-fold greater activity using the pre-miRNA DICER substrate. RISC distinguished the guide strand of the siRNA from the passenger strand and specifically incorporated the guide strand. ATP was not required for miRNA processing, RISC assembly, or multiple rounds of AGO2-mediated target RNA cleavage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16271387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Giraldez, A. J., Mishima, Y., Rihel, J., Grocock, R. J., Van Dongen, S., Inoue, K., Enright, A. J., Schier, A. F. <strong>Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs.</strong> Science 312: 75-79, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16484454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16484454</a>] [<a href="https://doi.org/10.1126/science.1122689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16484454">Giraldez et al. (2006)</a> found that zebrafish embryos deficient for maternal and zygotic Dicer activity cannot generate mature miRNAs. These mutants displayed defects during gastrulation and brain morphogenesis that were rescued by injection of processed miRNAs belonging to the miR430 family (homologous to human miR302A, <a href="/entry/614596">614596</a>). <a href="#19" class="mim-tip-reference" title="Giraldez, A. J., Mishima, Y., Rihel, J., Grocock, R. J., Van Dongen, S., Inoue, K., Enright, A. J., Schier, A. F. <strong>Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs.</strong> Science 312: 75-79, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16484454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16484454</a>] [<a href="https://doi.org/10.1126/science.1122689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16484454">Giraldez et al. (2006)</a> used a microarray approach and in vivo target validation to determine that miR430 regulates several hundred target mRNA molecules in the zebrafish zygote and embryo. Most targets are maternally expressed mRNAs that accumulate in the absence of miR430. <a href="#19" class="mim-tip-reference" title="Giraldez, A. J., Mishima, Y., Rihel, J., Grocock, R. J., Van Dongen, S., Inoue, K., Enright, A. J., Schier, A. F. <strong>Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs.</strong> Science 312: 75-79, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16484454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16484454</a>] [<a href="https://doi.org/10.1126/science.1122689" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16484454">Giraldez et al. (2006)</a> also showed that miR430 accelerated the deadenylation of target mRNAs. They concluded that miR430 facilitates the deadenylation and clearance of maternal mRNAs during early embryogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16484454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#55" class="mim-tip-reference" title="Tam, O. H., Aravin, A. A., Stein, P., Girard, A., Murchison, E. P., Cheloufi, S., Hodges, E., Anger, M., Sachidanandam, R., Schultz, R. M., Hannon, G. J. <strong>Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.</strong> Nature 453: 534-538, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404147</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18404147[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18404147">Tam et al. (2008)</a> showed that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endo-siRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endo-siRNA targets, demonstrating their regulatory activity. <a href="#55" class="mim-tip-reference" title="Tam, O. H., Aravin, A. A., Stein, P., Girard, A., Murchison, E. P., Cheloufi, S., Hodges, E., Anger, M., Sachidanandam, R., Schultz, R. M., Hannon, G. J. <strong>Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.</strong> Nature 453: 534-538, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404147</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18404147[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature06904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18404147">Tam et al. (2008)</a> concluded that their findings indicated a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonaute (see <a href="/entry/607355">607355</a>)-mediated catalysis in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18404147" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using mouse oocytes, <a href="#60" class="mim-tip-reference" title="Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi-Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., Surani, M. A., Sakaki, Y., Sasaki, H. <strong>Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.</strong> Nature 453: 539-543, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404146</a>] [<a href="https://doi.org/10.1038/nature06908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18404146">Watanabe et al. (2008)</a> demonstrated that endogenous siRNAs are derived from naturally occurring double-stranded RNAs (dsRNAs) and have roles in the regulation of gene expression. By means of deep sequencing, <a href="#60" class="mim-tip-reference" title="Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi-Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., Surani, M. A., Sakaki, Y., Sasaki, H. <strong>Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.</strong> Nature 453: 539-543, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404146</a>] [<a href="https://doi.org/10.1038/nature06908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18404146">Watanabe et al. (2008)</a> identified a large number of both approximately 25- to 27-nucleotide Piwi-interacting RNAs (piRNAs) and approximately 21-nucleotide siRNAs corresponding to mRNAs or retrotransposons in growing oocytes. piRNAs are bound to Mili (<a href="/entry/610310">610310</a>) and have a role in the regulation of retrotransposons. siRNAs are exclusively mapped to retrotransposons or other genomic regions that produce transcripts capable of forming double-stranded RNA structures. Inverted repeat structures, bidirectional transcription, and antisense transcripts from various loci are sources of the double-stranded RNAs. Some precursor transcripts of siRNAs are derived from expressed pseudogenes, indicating that one role of pseudogenes is to adjust the level of the founding source mRNA through RNAi. <a href="#60" class="mim-tip-reference" title="Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi-Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., Surani, M. A., Sakaki, Y., Sasaki, H. <strong>Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.</strong> Nature 453: 539-543, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404146</a>] [<a href="https://doi.org/10.1038/nature06908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18404146">Watanabe et al. (2008)</a> showed that loss of Dicer or Ago2 (<a href="/entry/606229">606229</a>) resulted in decreased levels of siRNAs and increased levels of retrotransposon and protein-coding transcripts complementary to the siRNAs. Thus, <a href="#60" class="mim-tip-reference" title="Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi-Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., Surani, M. A., Sakaki, Y., Sasaki, H. <strong>Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.</strong> Nature 453: 539-543, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404146</a>] [<a href="https://doi.org/10.1038/nature06908" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18404146">Watanabe et al. (2008)</a> concluded that the RNA interference (RNAi) pathway regulates both protein-coding transcripts and retrotransposons in mouse oocytes. They also concluded that their results revealed a role for endogenous siRNAs in mammalian oocytes and showed that organisms lacking RNA-dependent RNA polymerase (RdRP) activity can produce functional endogenous siRNAs from naturally occurring double-stranded RNAs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18404146" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Ghildiyal, M., Seitz, H., Horwich, M. D., Li, C., Du, T., Lee, S., Xu, J., Kittler, E. L. W., Zapp, M. L., Weng, Z., Zamore, P. D. <strong>Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.</strong> Science 320: 1077-1081, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18403677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18403677</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18403677[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1157396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18403677">Ghildiyal et al. (2008)</a> independently identified 21-nucleotide endo-siRNAs that corresponded to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. <a href="#18" class="mim-tip-reference" title="Ghildiyal, M., Seitz, H., Horwich, M. D., Li, C., Du, T., Lee, S., Xu, J., Kittler, E. L. W., Zapp, M. L., Weng, Z., Zamore, P. D. <strong>Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.</strong> Science 320: 1077-1081, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18403677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18403677</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18403677[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1157396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18403677">Ghildiyal et al. (2008)</a> also detected endo-siRNAs complementary to mRNAs; these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs required the siRNA-generating ribonuclease Dicer2 and the RNA interference effector protein Ago2. <a href="#18" class="mim-tip-reference" title="Ghildiyal, M., Seitz, H., Horwich, M. D., Li, C., Du, T., Lee, S., Xu, J., Kittler, E. L. W., Zapp, M. L., Weng, Z., Zamore, P. D. <strong>Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.</strong> Science 320: 1077-1081, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18403677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18403677</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18403677[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1157396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18403677">Ghildiyal et al. (2008)</a> proposed that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germline. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18403677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Kawamura, Y., Saito, K., Kin, T., Ono, Y., Asai, K., Sunohara, T., Okada, T. N., Siomi, M. C., Siomi, H. <strong>Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells.</strong> Nature 453: 793-797, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463636</a>] [<a href="https://doi.org/10.1038/nature06938" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463636">Kawamura et al. (2008)</a> showed that in cultured Drosophila S2 cells, AGO2 associated with endogenous small RNAs of 20-22 nucleotides in length, which they had collectively named endogenous short interfering RNAs (esiRNAs). EsiRNAs can be divided into 2 groups: one that mainly corresponds to a subset of retrotransposons, and the other that arises from stem-loop structures. EsiRNAs are produced in a Dicer-2-dependent manner from distinctive genomic loci, are modified at the 3-prime ends, and can direct AGO2 to cleave target RNAs. Mutations in Dicer-2 caused an increase in retrotransposon transcripts. <a href="#29" class="mim-tip-reference" title="Kawamura, Y., Saito, K., Kin, T., Ono, Y., Asai, K., Sunohara, T., Okada, T. N., Siomi, M. C., Siomi, H. <strong>Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells.</strong> Nature 453: 793-797, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463636</a>] [<a href="https://doi.org/10.1038/nature06938" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463636">Kawamura et al. (2008)</a> concluded that, together, their findings indicate that different types of small RNAs and Argonautes are used to repress retrotransposons in germline and somatic cells in Drosophila. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18463636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Czech, B., Malone, C. D., Zhou, R., Stark, A., Schlingeheyde, C., Dus, M., Perrimon, N., Kellis, M., Wohlschlegel, J. A., Sachidanandam, R., Hannon, G. J., Brennecke, J. <strong>An endogenous small interfering RNA pathway in Drosophila.</strong> Nature 453: 798-802, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463631[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463631">Czech et al. (2008)</a> independently showed that Drosophila generated endogenous small interfering RNAs in both gonadal and somatic tissues. Production of these RNAs requires Dicer-2, but a subset depends preferentially on Loquacious (TARBP2; <a href="/entry/605053">605053</a>) rather than the canonical Dicer-2 partner, R2D2. EsiRNAs arose both from the convergent transcription units and from structured genomic loci in a tissue-specific fashion. They predominantly join AGO2 and have the capacity, as a class, to target both protein-coding genes and mobile elements. <a href="#9" class="mim-tip-reference" title="Czech, B., Malone, C. D., Zhou, R., Stark, A., Schlingeheyde, C., Dus, M., Perrimon, N., Kellis, M., Wohlschlegel, J. A., Sachidanandam, R., Hannon, G. J., Brennecke, J. <strong>An endogenous small interfering RNA pathway in Drosophila.</strong> Nature 453: 798-802, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463631[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463631">Czech et al. (2008)</a> concluded that these observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18463631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Okamura, K., Chung, W.-J., Ruby, J. G., Guo, H., Bartel, D. P., Lai, E. C. <strong>The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs.</strong> Nature 453: 803-806, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463630[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463630">Okamura et al. (2008)</a> reported that siRNAs derived from long hairpin RNA genes (hpRNA) program Slicer complexes that can repress endogenous target transcripts. The Drosophila hpRNA pathway is a hybrid mechanism that combines canonical RNA interference factors Dicer-2, Hen1 (C1ORF59; <a href="/entry/612178">612178</a>), and AGO2 with a canonical microRNA factor Loquacious to generate approximately 21-nucleotide siRNAs. <a href="#45" class="mim-tip-reference" title="Okamura, K., Chung, W.-J., Ruby, J. G., Guo, H., Bartel, D. P., Lai, E. C. <strong>The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs.</strong> Nature 453: 803-806, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463630[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature07015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18463630">Okamura et al. (2008)</a> concluded that these novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biologic usage of endogenous RNA interference in Drosophila. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18463630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Merritt, W. M., Lin, Y. G., Han, L. Y., Kamat, A. A., Spannuth, W. A., Schmandt, R., Urbauer, D., Pennacchio, L. A., Cheng, J.-F., Nick, A. M., Deavers, M. T., Mourad-Zeidan, A., and 10 others. <strong>Dicer, Drosha, and outcomes in patients with ovarian cancer.</strong> New Eng. J. Med. 359: 2641-2650, 2008. Note: Erratum: New Eng. J. Med. 363: 1877 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19092150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19092150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19092150[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa0803785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19092150">Merritt et al. (2008)</a> observed decreased mRNA and protein expression of DICER1 and DROSHA (RNASEN; <a href="/entry/608828">608828</a>) in 60 and 51%, respectively, of 111 invasive epithelial ovarian cancer (<a href="/entry/167000">167000</a>) specimens. Low DICER1 expression was significantly associated with advanced tumor stage (p = 0.007), and low DROSHA expression with suboptimal surgical cytoreduction (p = 0.02). Cancer specimens with both high DICER1 expression and high DROSHA expression were associated with increased median survival. Statistical analysis showed that low DICER1 expression was associated with decreased survival. Although rare missense variants were found in both genes, the presence or absence did not correlate with the level of expression. Functional assays indicated that gene silencing with shRNA, but not siRNA, may be impaired in cells with low DICER1 expression. The findings implicated a component of the RNA-interference machinery, which regulates gene expression, in the pathogenesis of ovarian cancer. <a href="#39" class="mim-tip-reference" title="Merritt, W. M., Urbauer, D. L., Sood, A. K. <strong>Reply to Kobel et al. (Letter)</strong> New Eng. J. Med. 360: 1151 only, 2009."None>Merritt et al. (2009)</a> noted that 109 of the 111 samples used in the 2008 study had serous histologic features, of which 93 were high-grade and 16 low-grade tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19092150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By multiple sequence alignment, <a href="#13" class="mim-tip-reference" title="Forman, J. J., Legesse-Miller, A., Coller, H. A. <strong>A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence.</strong> Proc. Nat. Acad. Sci. 105: 14879-14884, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18812516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18812516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18812516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0803230105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18812516">Forman et al. (2008)</a> identified highly conserved LET7-binding sequences within the coding regions of multiple genes, including DICER. Cotransfection experiments with human embryonic kidney 293 cells revealed that LET7 downregulated an expression vector containing only the DICER coding sequence, which contains 3 LET7-binding sites. Synonymous mutations of these LET7-binding sites permitted DICER expression. Experiments with a human colorectal cancer cell line suggested that processing of LET7 pre-miRNA by DICER was required for downregulation of DICER through its coding sequence in a negative-feedback loop. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18812516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Nakagawa, A., Shi, Y., Kage-Nakadai, E., Mitani, S., Xue, D. <strong>Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease.</strong> Science 328: 327-334, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223951</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223951[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1182374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20223951">Nakagawa et al. (2010)</a> reported that inactivation of the C. elegans Dcr1 gene, which encodes the Dicer ribonuclease important for processing of small RNAs, compromises apoptosis and blocks apoptotic chromosome fragmentation. Dcr1 was cleaved by the Ced3 (<a href="/entry/601763">601763</a>) caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3-prime hydroxyl DNA breaks on chromosomes and promoted apoptosis. Thus, caspase-mediated activation of apoptotic DNA degradation is conserved. <a href="#42" class="mim-tip-reference" title="Nakagawa, A., Shi, Y., Kage-Nakadai, E., Mitani, S., Xue, D. <strong>Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease.</strong> Science 328: 327-334, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223951</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223951[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1182374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20223951">Nakagawa et al. (2010)</a> concluded that Dcr1 functions in fragmenting chromosomal DNA during apoptosis in addition to processing small RNAs, and undergoes a protease-mediated conversion from a ribonuclease to a deoxyribonuclease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20223951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#50" class="mim-tip-reference" title="Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T. <strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong> Nature 464: 852-857, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20305640">Raaijmakers et al. (2010)</a> demonstrated that deletion of Dicer1 specifically in mouse osteoprogenitors but not in mature osteoblasts disrupts the integrity of hematopoiesis. Myelodysplasia resulted and acute myelogenous leukemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds (<a href="/entry/607444">607444</a>), the gene mutated in Shwachman-Bodian-Diamond syndrome (<a href="/entry/260400">260400</a>), a human bone marrow failure and leukemia predisposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, <a href="#50" class="mim-tip-reference" title="Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T. <strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong> Nature 464: 852-857, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20305640">Raaijmakers et al. (2010)</a> concluded that perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation, and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, <a href="#50" class="mim-tip-reference" title="Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T. <strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong> Nature 464: 852-857, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature08851" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20305640">Raaijmakers et al. (2010)</a> concluded that primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20305640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In mice, Ago2 (EIF2C2; <a href="/entry/606229">606229</a>) is uniquely required for viability, and only this Argonaute family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, <a href="#5" class="mim-tip-reference" title="Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., Hannon, G. J. <strong>A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis.</strong> Nature 465: 584-589, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20424607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20424607</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20424607[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20424607">Cheloufi et al. (2010)</a> engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anemia. Examination of microRNAs and their potential targets revealed a loss of miR451 (<a href="/entry/612071">612071</a>), a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha, its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic center to generate an intermediate 3-prime end, which is then further trimmed. <a href="#5" class="mim-tip-reference" title="Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., Hannon, G. J. <strong>A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis.</strong> Nature 465: 584-589, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20424607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20424607</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20424607[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09092" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20424607">Cheloufi et al. (2010)</a> concluded that their findings linked the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20424607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#54" class="mim-tip-reference" title="Su, X., Chakravarti, D., Cho, M. S., Liu, L., Gi, Y. J., Lin, Y.-L., Leung, M. L., El-Naggar, A., Creighton, C. J., Suraokar, M. B., Wistuba, I., Flores, E. R. <strong>TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs.</strong> Nature 467: 986-990, 2010. Note: Erratum: Nature 632: E2, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20962848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20962848</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20962848[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20962848">Su et al. (2010)</a> showed that TAp63 (<a href="/entry/603273">603273</a>) suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR130b (<a href="/entry/613682">613682</a>) to suppress metastasis. Metastatic mouse and human tumors deficient in TAp63 express Dicer at very low levels, and <a href="#54" class="mim-tip-reference" title="Su, X., Chakravarti, D., Cho, M. S., Liu, L., Gi, Y. J., Lin, Y.-L., Leung, M. L., El-Naggar, A., Creighton, C. J., Suraokar, M. B., Wistuba, I., Flores, E. R. <strong>TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs.</strong> Nature 467: 986-990, 2010. Note: Erratum: Nature 632: E2, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20962848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20962848</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20962848[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20962848">Su et al. (2010)</a> found that modulation of expression of Dicer and miR130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. <a href="#54" class="mim-tip-reference" title="Su, X., Chakravarti, D., Cho, M. S., Liu, L., Gi, Y. J., Lin, Y.-L., Leung, M. L., El-Naggar, A., Creighton, C. J., Suraokar, M. B., Wistuba, I., Flores, E. R. <strong>TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs.</strong> Nature 467: 986-990, 2010. Note: Erratum: Nature 632: E2, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20962848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20962848</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20962848[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20962848">Su et al. (2010)</a> concluded that their data provided a novel understanding of the roles of TAp63 in tumor and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR130b, and may have implications for the many processes regulated by miRNAs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20962848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#48" class="mim-tip-reference" title="Park, J.-E., Heo, I., Tian, Y., Simanshu, D. K., Chang, H., Jee, D., Patel, D. J., Kim, V. N. <strong>Dicer recognizes the 5-prime end of RNA for efficient and accurate processing.</strong> Nature 475: 201-205, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21753850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21753850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21753850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21753850">Park et al. (2011)</a> reported that human DICER anchors not only the 3-prime end of microRNAs but also the 5-prime end, with the cleavage site determined mainly by the distance (approximately 22 nucleotides) from the 5-prime end (5-prime counting rule). This cleavage requires a 5-prime-terminal phosphate group. Further, <a href="#48" class="mim-tip-reference" title="Park, J.-E., Heo, I., Tian, Y., Simanshu, D. K., Chang, H., Jee, D., Patel, D. J., Kim, V. N. <strong>Dicer recognizes the 5-prime end of RNA for efficient and accurate processing.</strong> Nature 475: 201-205, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21753850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21753850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21753850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21753850">Park et al. (2011)</a> identified a novel basic motif (5-prime pocket) in human DICER that recognizes the 5-prime phosphorylated end. The 5-prime counting rule and the 5-prime anchoring residues are conserved in Drosophila Dicer-1, but not in Giardia Dicer. Mutations in the 5-prime pocket reduce processing efficiency and alter cleavage sites in vitro. Consistently, miRNA biogenesis is perturbed in vivo when Dicer-null embryonic stem cells are replenished with the 5-prime-pocket mutant. Thus, <a href="#48" class="mim-tip-reference" title="Park, J.-E., Heo, I., Tian, Y., Simanshu, D. K., Chang, H., Jee, D., Patel, D. J., Kim, V. N. <strong>Dicer recognizes the 5-prime end of RNA for efficient and accurate processing.</strong> Nature 475: 201-205, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21753850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21753850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21753850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature10198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21753850">Park et al. (2011)</a> concluded that 5-prime end recognition by DICER is important for the precise and effective biogenesis of miRNAs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21753850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Francia, S., Michelini, F., Saxena, A., Tang, D., de Hoon, M., Anelli, V., Mione, M., Carninci, P., d'Adda di Fagagna, F. <strong>Site-specific DICER and DROSHA RNA products control the DNA-damage response.</strong> Nature 488: 231-235, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22722852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22722852</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22722852[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22722852">Francia et al. (2012)</a> demonstrated in human, mouse, and zebrafish that DICER and DROSHA (<a href="/entry/608828">608828</a>), but not downstream elements of the RNAi pathway, are necessary to activate the DNA damage response (DDR) upon exogenous DNA damage and oncogene-induced genotoxic stress, as studied by DDR foci formation and by checkpoint assays. DDR foci are sensitive to RNase A treatment, and DICER- and DROSHA-dependent RNA products are required to restore DDR foci in RNase-A-treated cells. Through RNA deep sequencing and the study of DDR activation at a single inducible DNA double-strand break, <a href="#15" class="mim-tip-reference" title="Francia, S., Michelini, F., Saxena, A., Tang, D., de Hoon, M., Anelli, V., Mione, M., Carninci, P., d'Adda di Fagagna, F. <strong>Site-specific DICER and DROSHA RNA products control the DNA-damage response.</strong> Nature 488: 231-235, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22722852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22722852</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22722852[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22722852">Francia et al. (2012)</a> demonstrated that DDR foci formation requires site-specific DICER- and DROSHA-dependent small RNAs, named DDRNAs, which act in a MRE11-RAD50-NBS1-complex (see <a href="/entry/602667">602667</a>)-dependent manner. DDRNAs, either chemically synthesized or in vitro generated by DICER cleavage, are sufficient to restore the DDR in RNase-A-treated cells, also in the absence of other cellular RNAs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22722852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., Kleinman, M. E., Ponicsan, S. L., Hauswirth, W. W., Chiodo, V. A., Kariko, K., Yoo, J. W., and 30 others. <strong>DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration.</strong> Nature 471: 325-330, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21297615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21297615</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21297615[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21297615">Kaneko et al. (2011)</a> showed that DICER1 is reduced in the retinal pigment epithelium (RPE) of humans with geographic atrophy (see <a href="/entry/603075">603075</a>) and that conditional ablation of DICER1, but not of 7 other microRNA processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induced accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA was increased in the RPE of humans with geographic atrophy, and this pathogenic RNA induced human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevented DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA could not induce RPE degeneration in mice. <a href="#27" class="mim-tip-reference" title="Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., Kleinman, M. E., Ponicsan, S. L., Hauswirth, W. W., Chiodo, V. A., Kariko, K., Yoo, J. W., and 30 others. <strong>DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration.</strong> Nature 471: 325-330, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21297615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21297615</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21297615[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21297615">Kaneko et al. (2011)</a> concluded that their findings revealed an miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, showed that Alu RNA can directly cause human pathology, and identified new targets for a major cause of blindness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21297615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using mouse and human RPE cells and mice lacking various genes, <a href="#56" class="mim-tip-reference" title="Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., Albuquerque, R. J. C., Hauswirth, W. W., and 17 others. <strong>DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88.</strong> Cell 149: 847-859, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22541070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22541070</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22541070[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2012.03.036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22541070">Tarallo et al. (2012)</a> showed that a DICER1 deficit or Alu RNA exposure activated the NLRP3 (<a href="/entry/606416">606416</a>) inflammasome, triggering Toll-like receptor-independent MYD88 (<a href="/entry/602170">602170</a>) signaling via IL18 (<a href="/entry/600953">600953</a>) in the RPE. Inhibition of inflammasome components, MYD88, or IL18 prevented RPE degeneration induced by DICER1 loss or Alu RNA exposure. Because RPE in human geographic atrophy contained elevated NLRP3, PYCARD (<a href="/entry/606838">606838</a>), and IL18, <a href="#56" class="mim-tip-reference" title="Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., Albuquerque, R. J. C., Hauswirth, W. W., and 17 others. <strong>DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88.</strong> Cell 149: 847-859, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22541070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22541070</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22541070[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.cell.2012.03.036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22541070">Tarallo et al. (2012)</a> suggested targeting this pathway for prevention and/or treatment of geographic atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22541070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#33" class="mim-tip-reference" title="Li, Y., Lu, J., Han, Y., Fan, X., Ding, S.-W. <strong>RNA interference functions as an antiviral immunity mechanism in mammals.</strong> Science 342: 231-234, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24115437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24115437</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24115437[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1241911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24115437">Li et al. (2013)</a> showed that infection of hamster cells and suckling mice by Nodamura virus, a mosquito-transmissible RNA virus, requires RNA interference suppression by its B2 protein. Loss of B2 expression or its suppressor activity leads to abundant production of viral siRNAs and rapid clearance of the mutant viruses in mice. However, viral small RNAs detected during virulent infection by Nodamura virus do not have the properties of canonical siRNAs. <a href="#35" class="mim-tip-reference" title="Maillard, P. V., Ciaudo, C., Marchais, A., Li, Y., Jay, F., Ding, S. W., Voinnet, O. <strong>Antiviral RNA interference in mammalian cells.</strong> Science 342: 235-238, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24115438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24115438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24115438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1241930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24115438">Maillard et al. (2013)</a> demonstrated that undifferentiated mouse cells infected with encephalomyocarditis virus or Nodamura virus accumulate approximately 22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral double-strand RNA (dsRNA) replication intermediates, incorporate into Ago2 (<a href="/entry/606229">606229</a>), are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a Nodamura virus-encoded suppressor of RNAi that antagonizes Dicer during authentic infections reduces Nodamura virus accumulation, which is rescued in RNAi-deficient mouse cells. <a href="#35" class="mim-tip-reference" title="Maillard, P. V., Ciaudo, C., Marchais, A., Li, Y., Jay, F., Ding, S. W., Voinnet, O. <strong>Antiviral RNA interference in mammalian cells.</strong> Science 342: 235-238, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24115438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24115438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24115438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1241930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24115438">Maillard et al. (2013)</a> concluded that antiviral RNA interference operates in mammalian cells. <a href="#33" class="mim-tip-reference" title="Li, Y., Lu, J., Han, Y., Fan, X., Ding, S.-W. <strong>RNA interference functions as an antiviral immunity mechanism in mammals.</strong> Science 342: 231-234, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24115437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24115437</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24115437[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1241911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24115437">Li et al. (2013)</a> concluded that their findings and those of <a href="#35" class="mim-tip-reference" title="Maillard, P. V., Ciaudo, C., Marchais, A., Li, Y., Jay, F., Ding, S. W., Voinnet, O. <strong>Antiviral RNA interference in mammalian cells.</strong> Science 342: 235-238, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24115438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24115438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24115438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1241930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24115438">Maillard et al. (2013)</a> illustrated that Dicer-dependent processing of dsRNA viral replication intermediates into successive siRNAs is a conserved mammalian immune response to infection by 2 distinct positive-strand RNA viruses. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24115438+24115437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In mice, <a href="#10" class="mim-tip-reference" title="Dias, C., Feng, J., Sun, H., Shao, N., Mazei-Robison, M. S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonte, B., Ribeiro, E., Liu, X., Kennedy, P., and 11 others. <strong>Beta-catenin mediates stress resilience through Dicer1/microRNA regulation.</strong> Nature 516: 51-55, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25383518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25383518</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25383518[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature13976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25383518">Dias et al. (2014)</a> showed that beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>) mediates proresilient and anxiolytic effects in the nucleus accumbens, mediated by D2-type medium spiny neurons. Using genomewide beta-catenin enrichment mapping, <a href="#10" class="mim-tip-reference" title="Dias, C., Feng, J., Sun, H., Shao, N., Mazei-Robison, M. S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonte, B., Ribeiro, E., Liu, X., Kennedy, P., and 11 others. <strong>Beta-catenin mediates stress resilience through Dicer1/microRNA regulation.</strong> Nature 516: 51-55, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25383518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25383518</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25383518[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature13976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25383518">Dias et al. (2014)</a> identified Dicer1 as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin from nucleus accumbens in the context of chronic stress revealed beta-catenin-dependent microRNA regulation associated with resilience. <a href="#10" class="mim-tip-reference" title="Dias, C., Feng, J., Sun, H., Shao, N., Mazei-Robison, M. S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonte, B., Ribeiro, E., Liu, X., Kennedy, P., and 11 others. <strong>Beta-catenin mediates stress resilience through Dicer1/microRNA regulation.</strong> Nature 516: 51-55, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25383518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25383518</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25383518[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature13976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25383518">Dias et al. (2014)</a> concluded that these findings established beta-catenin as a critical regulator in the development of behavioral resilience, activating a network that includes DICER1 and downstream microRNAs. The authors stated that this evidence presented a foundation for the development of novel therapeutic targets to promote stress resilience. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25383518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Copy Number Variation in Cancer</em></strong></p><p>
|
|
By examining DNA copy number in 283 known miRNA genes, <a href="#64" class="mim-tip-reference" title="Zhang, L., Huang, J., Yang, N., Greshock, J., Megraw, M. S., Giannakakis, A., Liang, S., Naylor, T. L., Barchetti, A., Ward, M. R., Yao, G., Medina, A., O'Brien-Jenkins, A., Katsaros, D., Hatzigeorgiou, A., Gimotty, P. A., Weber, B. L., Coukos, G. <strong>MicroRNAs exhibit high frequency genomic alterations in human cancer.</strong> Proc. Nat. Acad. Sci. 103: 9136-9141, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16754881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16754881</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16754881[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0508889103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16754881">Zhang et al. (2006)</a> found a high proportion of copy number abnormalities in 227 human ovarian cancer, breast cancer, and melanoma specimens. Changes in miRNA copy number correlated with miRNA express. They also found a high frequency of copy number abnormalities of DICER1, AGO2 (<a href="/entry/606229">606229</a>), and other miRNA-associated genes in these cancers. <a href="#64" class="mim-tip-reference" title="Zhang, L., Huang, J., Yang, N., Greshock, J., Megraw, M. S., Giannakakis, A., Liang, S., Naylor, T. L., Barchetti, A., Ward, M. R., Yao, G., Medina, A., O'Brien-Jenkins, A., Katsaros, D., Hatzigeorgiou, A., Gimotty, P. A., Weber, B. L., Coukos, G. <strong>MicroRNAs exhibit high frequency genomic alterations in human cancer.</strong> Proc. Nat. Acad. Sci. 103: 9136-9141, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16754881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16754881</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16754881[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0508889103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16754881">Zhang et al. (2006)</a> concluded that copy number alterations of miRNAs and their regulatory genes are highly prevalent in cancer and may account partly for the frequent miRNA gene deregulation reported in several tumor types. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16754881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Pleuropulmonary Blastoma</em></strong></p><p>
|
|
<a href="#24" class="mim-tip-reference" title="Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J. <strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong> Science 325: 965 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556464</a>] [<a href="https://doi.org/10.1126/science.1174334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556464">Hill et al. (2009)</a> demonstrated 10 loss-of-function and 1 missense mutation in the DICER1 gene (see, e.g., <a href="#0001">606241.0001</a>-<a href="#0005">606241.0005</a>) leading to pleuropulmonary blastoma (PPB; <a href="/entry/601200">601200</a>). In patients with tumors, there was loss of the wildtype allele within malignant areas in 6 of 7 the cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bahubeshi, A., Bal, N., Rio Frio, T., Hamel, N., Pouchet, C., Yilmaz, A., Bouron-Dal Soglio, D., Williams, G. M., Tischkowitz, M., Priest, J. R., Foulkes, W. D. <strong>Germline DICER1 mutations and familial cystic nephroma.</strong> J. Med. Genet. 47: 863-866, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21036787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21036787</a>] [<a href="https://doi.org/10.1136/jmg.2010.081216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21036787">Bahubeshi et al. (2010)</a> reported 2 unrelated families with cystic nephroma with or without PPB associated with different heterozygous mutations in the DICER1 gene in each family (see, e.g., <a href="#0006">606241.0006</a>). The findings added cystic nephroma to the phenotypic spectrum of PPB. Loss of heterozygosity at the DICER1 locus was not observed in tumor tissue. No germline DICER1 mutations were found in 50 children with Wilms tumor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21036787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Cervical Embryonal Rhabdomyosarcoma</em></strong></p><p>
|
|
<a href="#14" class="mim-tip-reference" title="Foulkes, W. D., Bahubeshi, A., Hamel, N., Pasini, B., Asioli, S., Baynam, G., Choong, C. S., Charles, A., Frieder, R. P., Dishop, M. K., Graf, N., Ekim, M., Bouron-Dal Soglio, D., Arseneau, J., Young, R. H., Sabbaghian, N., Srivastava, A., Tischkowitz, M. D., Priest, J. R. <strong>Extending the phenotypes associated with DICER1 mutations.</strong> Hum. Mutat. 32: 1381-1384, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21882293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21882293</a>] [<a href="https://doi.org/10.1002/humu.21600" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21882293">Foulkes et al. (2011)</a> stated that 40 different heterozygous germline mutations in DICER1 had been reported worldwide in 42 probands who developed pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors, or multinodular goiter as children or young adults. <a href="#14" class="mim-tip-reference" title="Foulkes, W. D., Bahubeshi, A., Hamel, N., Pasini, B., Asioli, S., Baynam, G., Choong, C. S., Charles, A., Frieder, R. P., Dishop, M. K., Graf, N., Ekim, M., Bouron-Dal Soglio, D., Arseneau, J., Young, R. H., Sabbaghian, N., Srivastava, A., Tischkowitz, M. D., Priest, J. R. <strong>Extending the phenotypes associated with DICER1 mutations.</strong> Hum. Mutat. 32: 1381-1384, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21882293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21882293</a>] [<a href="https://doi.org/10.1002/humu.21600" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21882293">Foulkes et al. (2011)</a> reported DICER1 mutations in 7 additional families manifesting uterine cervix embryonal rhabdomyosarcoma (CERMS, 4 cases), primitive neuroectodermal tumor (CPNET, 1 case), Wilms tumor (3 cases), pulmonary sequestration (1 case), and juvenile intestinal polyp (1 case). One mutation carrier in 1 family had complex cardiac defects, including transposition of the great arteries, bicuspid pulmonary valve, atrial septal defect, and small patent ductus arteriosus, and a mutation carrier in another family had pulmonary sequestration. Examination of tumor tissue from several patients did not show loss of heterozygosity for DICER1, indicating that some different second events must be required for tumor formation. However, the findings indicated that germline DICER1 mutations serve as a conditioning context for the development of multiple tumor types. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21882293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Multinodular Goiter 1, with or without Sertoli-Leydig Cell Tumors</em></strong></p><p>
|
|
In affected members of 5 unrelated families with autosomal dominant multinodular goiter with or without Sertoli-Leydig cell tumors (MNG1; <a href="/entry/138800">138800</a>), <a href="#52" class="mim-tip-reference" title="Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others. <strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong> J.A.M.A. 305: 68-77, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205968">Rio Frio et al. (2011)</a> identified 5 different heterozygous mutations in the DICER1 gene (see, e.g., <a href="#0007">606241.0007</a>-<a href="#0010">606241.0010</a>). Four of the families had previously been reported by <a href="#44" class="mim-tip-reference" title="O'Brien, P. K., Wilansky, D. L. <strong>Familial thyroid nodulation and arrhenoblastoma.</strong> Am. J. Clin. Path. 75: 578-581, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261577</a>] [<a href="https://doi.org/10.1093/ajcp/75.4.578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6261577">O'Brien and Wilansky (1981)</a>, <a href="#43" class="mim-tip-reference" title="Niedziela, M. <strong>Virilizing ovarian tumor in a 14-year-old female with a prior familial multinodular goiter.</strong> Pediat. Blood Cancer 51: 543-545, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570301</a>] [<a href="https://doi.org/10.1002/pbc.21675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18570301">Niedziela (2008)</a>, <a href="#3" class="mim-tip-reference" title="Bignell, G. R., Canzian, F., Shayeghi, M., Stark, M., Shugart, Y. Y., Biggs, P., Mangion, J., Hamoudi, R., Rosenblatt, J., Buu, P., Sun, S., Stoffer, S. S., Goldgar, D. E., Romeo, G., Houlston, R. S., Narod, S. A., Stratton, M. R., Foulkes, W. D. <strong>Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.</strong> Am. J. Hum. Genet. 61: 1123-1130, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345104</a>] [<a href="https://doi.org/10.1086/301610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9345104">Bignell et al. (1997)</a>, and <a href="#11" class="mim-tip-reference" title="Druker, H. A., Kasprzak, L., Begin, L. R., Jothy, S., Narod, S. A., Foulkes, W. D. <strong>Family with Graves disease, multinodular goiter, nonmedullary thyroid carcinoma, and alveolar rhabdomyosarcoma.</strong> Am. J. Med. Genet. 72: 30-33, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9295070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9295070</a>]" pmid="9295070">Druker et al. (1997)</a>. Studies of both types of tumors from several families showed no loss of heterozygosity at the DICER1 locus. Goiter tissue showed mixed immunostaining results, with some tissues showing no DICER1 protein staining and other tissues showing clear cytoplasmic staining. RNA studies from patient lymphoblasts showed perturbations of miRNA compared to controls, suggesting a dysregulation of gene expression patterns. In particular, LET7A (<a href="/entry/605386">605386</a>) and miR345 were both decreased in DICER1-related goiter tissue. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21205968+9345104+6261577+18570301+9295070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Pineoblastoma</em></strong></p><p>
|
|
<a href="#53" class="mim-tip-reference" title="Sabbaghian, N., Hamel, N., Srivastava, A., Albrecht, S., Priest, J. R., Foulkes, W. D. <strong>Germline DICER1 mutation and associated loss of heterozygosity in a pineoblastoma.</strong> J. Med. Genet. 49: 417-419, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22717647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22717647</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-100898" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22717647">Sabbaghian et al. (2012)</a> reported a single patient with a highly aggressive pineoblastoma due to germline frameshift mutation in DICER1. This tumor had loss of heterozygosity with loss of function of the wildtype allele of DICER1. Interestingly, it is possible for a tumor to survive without any DICER1 activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22717647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Wilms Tumor</em></strong></p><p>
|
|
<a href="#51" class="mim-tip-reference" title="Rakheja, D., Chen, K. S., Liu, Y., Shukla, A. A., Schmid, V., Chang, T.-C., Khokhar, S., Wickiser, J. E., Karandikar, N. J., Malter, J. S., Mendell, J. T., Amatruda, J. F. <strong>Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours.</strong> Nature Commun. 5: 4802, 2014. Note: Electronic Article. Erratum: Nature Commun. 8: 16177, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25190313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25190313</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25190313[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ncomms5802" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25190313">Rakheja et al. (2014)</a> reported the whole-exome sequencing of 44 Wilms tumors (see WT1, <a href="/entry/194070">194070</a>), identifying missense mutations in the microRNA (miRNA)-processing enzymes DROSHA (<a href="/entry/608828">608828</a>) and DICER1, and novel mutations in MYCN (<a href="/entry/164840">164840</a>), SMARCA4 (<a href="/entry/603254">603254</a>), and ARID1A (<a href="/entry/603024">603024</a>). Examination of tumor miRNA expression, in vitro processing assays, and genomic editing in human cells demonstrated that DICER1 and DROSHA mutations influence miRNA processing through distinct mechanisms. DICER1 RNase IIIB mutations preferentially impair processing of miRNAs deriving from the 5-prime arm of pre-miRNA hairpins, while DROSHA RNase IIIB mutations globally inhibit miRNA biogenesis through a dominant-negative mechanism. Both DROSHA and DICER1 mutations impair expression of tumor-suppressing miRNAs, including the LET7 family (see <a href="/entry/605386">605386</a>), which are important regulators of MYCN, LIN28 (see <a href="/entry/611043">611043</a>), and other Wilms tumor oncogenes. <a href="#51" class="mim-tip-reference" title="Rakheja, D., Chen, K. S., Liu, Y., Shukla, A. A., Schmid, V., Chang, T.-C., Khokhar, S., Wickiser, J. E., Karandikar, N. J., Malter, J. S., Mendell, J. T., Amatruda, J. F. <strong>Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours.</strong> Nature Commun. 5: 4802, 2014. Note: Electronic Article. Erratum: Nature Commun. 8: 16177, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25190313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25190313</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25190313[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ncomms5802" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25190313">Rakheja et al. (2014)</a> concluded that these results provided insights into the mechanisms through which mutations in miRNA biogenesis components reprogram miRNA expression in human cancer and suggested that these defects define a distinct subclass of Wilms tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25190313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="Palculict, T. B., Ruteshouser, E. C., Fan, Y., Wang, W., Strong, L., Huff, V. <strong>Identification of germline DICER1 mutations and loss of heterozygosity in familial Wilms tumour.</strong> J. Med. Genet. 53: 385-388, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26566882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26566882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26566882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2015-103311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26566882">Palculict et al. (2016)</a> identified 2 different heterozygous germline mutations in the DICER1 gene in affected members from 2 unrelated families with familial Wilms tumors. Eleven individuals in 1 family carried a heterozygous G803R mutation that was identified by whole-genome sequencing and confirmed by Sanger sequencing. Four individuals in this family had Wilms tumor, diagnosed between 38 and 57 months of age. Tumor tissue available from 1 patient showed homozygosity for the G803R mutation and loss of heterozygosity at the DICER1 locus. Some individuals in this family had phenotypes of so-called DICER1 syndrome, including cysts in the thyroid, lung, and kidney. The proband from the second family with Wilms tumor carried a heterozygous frameshift mutation (Arg800fsTer5) that was identified by direct sequencing of the DICER1 gene in 47 families. Tumor samples were not available from the second family. Penetrance appeared to be incomplete. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26566882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>GLOW Syndrome</em></strong></p><p>
|
|
In 2 unrelated patients with developmental delay, overgrowth, bilateral cystic lung lesions, and Wilms tumor (GLOW; <a href="/entry/618272">618272</a>), <a href="#30" class="mim-tip-reference" title="Klein, S., Lee, H., Ghahremani, S., Kempert, P., Ischander, M., Teitell, M. A., Nelson, S. F., Martinez-Agosto, J. A. <strong>Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome.</strong> J. Med. Genet. 51: 294-302, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24676357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24676357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24676357[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-101943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24676357">Klein et al. (2014)</a> detected 2 missense mutations in the DICER1 gene (<a href="#0013">606241.0013</a> and <a href="#0014">606241.0014</a>) present in the mosaic state. Tissue abundance of the mutated DICER DNA ranged from 21 to 37% in patient 1 and 28 to 47% in patient 2 in blood, tumor, and unaffected kidney samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24676357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>MicroRNAs have a central role in the development of plants, nematodes, and flies. These miRNAs are produced by the Dicer1 enzyme, which is conserved from fungi to vertebrates. To study its role in vertebrate development, <a href="#61" class="mim-tip-reference" title="Wienholds, E., Koudijs, M. J., van Eeden, F. J. M., Cuppen, E., Plasterk, R. H. A. <strong>The microRNA-producing enzyme Dicer1 is essential for zebrafish development.</strong> Nature Genet. 35: 217-218, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14528306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14528306</a>] [<a href="https://doi.org/10.1038/ng1251" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14528306">Wienholds et al. (2003)</a> cloned the zebrafish dicer1 ortholog and applied a method for target-selected gene inactivation. They observed an initial build-up of miRNA levels, produced by maternal Dicer1, in homozygous dicer1 mutants, but miRNA accumulation stopped after a few days. This resulted in developmental arrest around day 10. The results indicated that miRNA-producing Dicer1 is essential for vertebrate development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14528306" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bernstein, E., Kim, S. Y., Carmell, M. A., Murchison, E. P., Alcorn, H., Li, M. Z., Mills, A. A., Elledge, S. J., Anderson, K. V., Hannon, G. J. <strong>Dicer is essential for mouse development.</strong> Nature Genet. 35: 215-216, 2003. Note: Erratum: Nature Genet. 35: 287 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14528307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14528307</a>] [<a href="https://doi.org/10.1038/ng1253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14528307">Bernstein et al. (2003)</a> disrupted the Dicer1 gene in mice. Loss of Dicer1 led to lethality early in development, with Dicer1-null embryos depleted of stem cells. Coupled with the inability to generate viable Dicer1-null embryonic stem (ES) cells, this suggested a role for Dicer and, by implication, the RNAi machinery in maintaining the stem cell population during early mouse development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14528307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By conditional gene targeting, <a href="#28" class="mim-tip-reference" title="Kanellopoulou, C., Muljo, S. A., Kung, A. L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D. M., Rajewsky, K. <strong>Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing.</strong> Genes Dev. 19: 489-501, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15713842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15713842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15713842[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1248505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15713842">Kanellopoulou et al. (2005)</a> disrupted the Dicer1 gene in mouse ES cells. Dicer-null ES cells were viable, despite being completely defective in RNA interference and generation of microRNAs. However, mutant ES cells displayed severe defects in differentiation both in vitro and in vivo. Epigenetic silencing of centromeric repeat sequences and expression of homologous small dsRNAs were markedly reduced. Reexpression of Dicer in knockout cells rescued these phenotypes. <a href="#28" class="mim-tip-reference" title="Kanellopoulou, C., Muljo, S. A., Kung, A. L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D. M., Rajewsky, K. <strong>Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing.</strong> Genes Dev. 19: 489-501, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15713842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15713842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15713842[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1248505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15713842">Kanellopoulou et al. (2005)</a> concluded that Dicer participates in multiple, fundamental biologic processes, ranging from stem cell differentiation to maintenance of centromeric heterochromatin structure and centromeric silencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15713842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#62" class="mim-tip-reference" title="Yi, R., O'Carroll, D., Pasolli, H. A., Zhang, Z., Dietrich, F. S., Tarakhovsky, A., Fuchs, E. <strong>Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs.</strong> Nature Genet. 38: 356-362, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16462742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16462742</a>] [<a href="https://doi.org/10.1038/ng1744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16462742">Yi et al. (2006)</a> cloned more than 100 miRNAs from skin and showed that epidermis and hair follicles differentially express discrete miRNA families. To explore the functional significance of this finding, they conditionally targeted Dicer1 gene ablation in embryonic skin precursors. Within the first week after loss of miRNA expression, cell fate specification and differentiation were not markedly impaired, and in the interfollicular epidermis, apoptosis was not markedly increased. Notably, however, developing hair germs evaginated rather than invaginated, thereby perturbing the epidermal organization. Thus, <a href="#62" class="mim-tip-reference" title="Yi, R., O'Carroll, D., Pasolli, H. A., Zhang, Z., Dietrich, F. S., Tarakhovsky, A., Fuchs, E. <strong>Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs.</strong> Nature Genet. 38: 356-362, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16462742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16462742</a>] [<a href="https://doi.org/10.1038/ng1744" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16462742">Yi et al. (2006)</a> characterized miRNAs in skin, the existence of which was hitherto unappreciated, and demonstrated their differential expression and importance in the morphogenesis of epithelial tissues within this vital organ. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16462742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Muljo, S. A., Ansel, K. M., Kanellopoulou, C., Livingston, D. M., Rao, A., Rajewsky, K. <strong>Aberrant T cell differentiation in the absence of Dicer.</strong> J. Exp. Med. 202: 261-269, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16009718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16009718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16009718[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20050678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16009718">Muljo et al. (2005)</a> found that conditional deletion of the mouse Dcr1 gene in the T-cell lineage resulted in impaired T-cell development and aberrant T-helper (Th) cell differentiation and cytokine production. Deletion of Dcr1 in thymus led to a severe block in CD8 (see <a href="/entry/186910">186910</a>)-positive T-cell development and reduced CD4 (<a href="/entry/186940">186940</a>)-positive T-cell numbers. The CD4-positive cells were defective in miRNA processing and, upon stimulation, proliferated poorly and underwent increased apoptosis. Dcr1-deficient Th cells preferentially expressed Ifng (<a href="/entry/147570">147570</a>), characteristic of helper cells of the Th1 lineage. Th2 cells lacking Dcr1 failed to silence Ifng expression. <a href="#40" class="mim-tip-reference" title="Muljo, S. A., Ansel, K. M., Kanellopoulou, C., Livingston, D. M., Rao, A., Rajewsky, K. <strong>Aberrant T cell differentiation in the absence of Dicer.</strong> J. Exp. Med. 202: 261-269, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16009718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16009718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16009718[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1084/jem.20050678" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16009718">Muljo et al. (2005)</a> proposed that the RNAi pathway may participate in epigenetic silencing of relevant genes during Th-cell lineage commitment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16009718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#59" class="mim-tip-reference" title="Wang, X.-H., Aliyari, R., Li, W.-X., Li, H.-W., Kim, K., Carthew, R., Atkinson, P., Ding, S.-W. <strong>RNA interference directs innate immunity against viruses in adult Drosophila.</strong> Science 312: 452-454, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16556799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16556799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16556799[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1125694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16556799">Wang et al. (2006)</a> demonstrated that an RNA interference pathway protects adult flies from infection by 2 evolutionarily diverse viruses. Their work also described a molecular framework for the viral immunity, in which viral double-stranded RNA produced during infection acts as the pathogen trigger whereas Drosophila Dicer-2 and Argonaute-2 (<a href="/entry/606228">606228</a>) act as host sensor and effector, respectively. <a href="#59" class="mim-tip-reference" title="Wang, X.-H., Aliyari, R., Li, W.-X., Li, H.-W., Kim, K., Carthew, R., Atkinson, P., Ding, S.-W. <strong>RNA interference directs innate immunity against viruses in adult Drosophila.</strong> Science 312: 452-454, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16556799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16556799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16556799[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1125694" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16556799">Wang et al. (2006)</a> concluded that their findings established a Drosophila model for studying the innate immunity against viruses in animals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16556799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Drosophila have 2 Dicer genes: Dcr1, which controls production of miRNA, and Dcr2, which controls production of siRNA. <a href="#17" class="mim-tip-reference" title="Galiana-Arnoux, D., Dostert, C., Schneemann, A., Hoffmann, J. A., Imler, J.-L. <strong>Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.</strong> Nature Immun. 7: 590-597, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16554838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16554838</a>] [<a href="https://doi.org/10.1038/ni1335" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16554838">Galiana-Arnoux et al. (2006)</a> found that Drosophila with a loss-of-function function mutation in Dcr2 were more susceptible to 3 different families of RNA viruses. The viral protein B2, a potent inhibitor of processing of double-stranded RNA, was required for infection and killing of Drosophila. <a href="#17" class="mim-tip-reference" title="Galiana-Arnoux, D., Dostert, C., Schneemann, A., Hoffmann, J. A., Imler, J.-L. <strong>Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.</strong> Nature Immun. 7: 590-597, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16554838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16554838</a>] [<a href="https://doi.org/10.1038/ni1335" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16554838">Galiana-Arnoux et al. (2006)</a> concluded that RNA interference mechanisms are important in controlling virus replication in Drosophila. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16554838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Murchison, E. P., Stein, P., Xuan, Z., Pan, H., Zhang, M. Q., Schultz, R. M., Hannon, G. J. <strong>Critical roles for Dicer in the female germline.</strong> Genes Dev. 21: 682-693, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17369401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17369401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17369401[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.1521307" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17369401">Murchison et al. (2007)</a> reported that targeted disruption of Dicer in mouse oocytes led to arrest in meiosis I with multiple disorganized spindles and severe chromosome congression defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17369401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To assess the role of miRNAs in cardiac development, <a href="#66" class="mim-tip-reference" title="Zhao, Y., Ransom, J. F., Li, A., Vedantham, V., von Drehle, M., Muth, A. N., Tsuchihashi, T., McManus, M. T., Schwartz, R. J., Srivastava, D. <strong>Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.</strong> Cell 129: 303-317, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17397913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17397913</a>] [<a href="https://doi.org/10.1016/j.cell.2007.03.030" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17397913">Zhao et al. (2007)</a> deleted Dicer in mouse heart. Mutant mice exhibited embryonic lethality by day 12.5, revealing an essential role for miRNA function in developing heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17397913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using gene-trap methods, <a href="#46" class="mim-tip-reference" title="Otsuka, M., Jing, Q., Georgel, P., New, L., Chen, J., Mols, J., Kang, Y. J., Jiang, Z., Du, X., Cook, R., Das, S. C., Pattnaik, A. K., Beutler, B., Han, J. <strong>Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression.</strong> Immunity 27: 123-134, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17613256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17613256</a>] [<a href="https://doi.org/10.1016/j.immuni.2007.05.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17613256">Otsuka et al. (2007)</a> obtained mice functionally deficient in Dicer1 that did not undergo embryonic lethality due to hypomorphic Dicer1 expression. Analysis of viral growth in peritoneal macrophages of these mice revealed susceptibility to vesicular stomatitis virus (VSV) and herpes simplex-1 virus, but not to other viruses tested. Susceptibility to VSV was not due to increased VSV cell entry nor to deficiencies in type I interferon (e.g., IFNA; <a href="/entry/147660">147660</a>) production or IFN responses. Reporter gene analysis of a mouse macrophage cell line transfected with plasmids containing VSV sequences showed that miR24 (see <a href="/entry/609705">609705</a>) and miR93 (<a href="/entry/612984">612984</a>), which were expressed in the both the cell line and in peritoneal macrophages, targeted VSV genes encoding a viral RNA-dependent polymerase and a polymerase cofactor, respectively. Further analysis indicated that miR24 and miR93 suppressed VSV propagation in mouse macrophages. VSV lacking the miR24 and miR93 target sites was more pathogenic in wildtype mice than wildtype VSV. <a href="#46" class="mim-tip-reference" title="Otsuka, M., Jing, Q., Georgel, P., New, L., Chen, J., Mols, J., Kang, Y. J., Jiang, Z., Du, X., Cook, R., Das, S. C., Pattnaik, A. K., Beutler, B., Han, J. <strong>Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression.</strong> Immunity 27: 123-134, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17613256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17613256</a>] [<a href="https://doi.org/10.1016/j.immuni.2007.05.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17613256">Otsuka et al. (2007)</a> concluded that impairment of miR24 and miR93 production due to Dicer1 deficiency results in increased susceptibility to VSV. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17613256" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Cuellar, T. L., Davis, T. H., Nelson, P. T., Loeb, G. B., Harfe, B. D., Ullian, E., McManus, M. T. <strong>Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration.</strong> Proc. Nat. Acad. Sci. 105: 5614-5619, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18385371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18385371</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18385371[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0801689105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18385371">Cuellar et al. (2008)</a> created transgenic mice with targeted ablation of the Dicer1 gene in postmitotic dopaminoceptive neurons and found that the mice developed ataxia, front and hind limb clasping, and decreased life span with death occurring between 10 to 12 weeks of age. Postmortem examination showed reduced brain size, a reduction in miRNAs in the striatum, and smaller striatal neurons. The striatum showed astrogliosis but not neurodegeneration or neuronal loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18385371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#31" class="mim-tip-reference" title="Kobayashi, T., Lu, J., Cobb, B. S., Rodda, S. J., McMahon, A. P., Schipani, E., Merkenschlager, M., Kronenberg, H. M. <strong>Dicer-dependent pathways regulate chondrocyte proliferation and differentiation.</strong> Proc. Nat. Acad. Sci. 105: 1949-1954, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18238902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18238902</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18238902[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0707900105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18238902">Kobayashi et al. (2008)</a> found that targeted deletion of Dicer1 in mouse cartilage resulted in progressive reduction in the proliferating pool of chondrocytes, leading to severe skeletal growth defects and premature death. Reduction of proliferating chondrocytes in Dicer1-null growth plates was caused by both decreased chondrocyte proliferation and accelerated differentiation into postmitotic hypertrophic chondrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18238902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Koralov, S. B., Muljo, S. A., Galler, G. R., Krek, A., Chakraborty, T., Kanellopoulou, C., Jensen, K., Cobb, B. S., Merkenschlager, M., Rajewsky, N., Rajewsky, K. <strong>Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage.</strong> Cell 132: 860-874, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18329371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18329371</a>] [<a href="https://doi.org/10.1016/j.cell.2008.02.020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18329371">Koralov et al. (2008)</a> conditionally deleted Dicer in mouse early B-cell progenitors and observed a block in the pro- to pre-B cell transition. Gene expression profiling identified an miR17-92 (see <a href="/entry/609416">609416</a>) signature in the 3-prime UTRs of genes upregulated in Dicer -/- pro-B cells, such as Bim (BCL2L11; <a href="/entry/603827">603827</a>). Ablation of Bim or transgenic expression of Bcl2 (<a href="/entry/151430">151430</a>) partially rescued B-cell development. Dicer deficiency had no detectable effect on the developmental V(D)J recombination program, but it did affect antibody diversification by increasing the diversity of Ig-kappa variable regions through increased N sequence insertion and changing Dh element usage in the variable regions of IgH chains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18329371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Chen, J.-F., Murchison, E. P., Tang, R., Callis, T. E., Tatsuguchi, M., Deng, Z., Rojas, M., Hammond, S. M., Schneider, M. D., Selzman, C. H., Meissner, G., Patterson, C., Hannon, G. J., Wang, D.-Z. <strong>Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.</strong> Proc. Nat. Acad. Sci. 105: 2111-2116, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18256189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18256189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18256189[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0710228105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18256189">Chen et al. (2008)</a> generated mice with cardiac-specific knockout of Dicer and observed rapidly progressive dilated cardiomyopathy (CMD; see <a href="/entry/115200">115200</a>), heart failure, and postnatal lethality. Dicer-mutant mice showed misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicated significantly reduced heart rates and decreased fractional shortening of Dicer-mutant hearts. Dicer expression was also found to be decreased in failing human hearts in end-stage CMD, and a significant increase in Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. <a href="#6" class="mim-tip-reference" title="Chen, J.-F., Murchison, E. P., Tang, R., Callis, T. E., Tatsuguchi, M., Deng, Z., Rojas, M., Hammond, S. M., Schneider, M. D., Selzman, C. H., Meissner, G., Patterson, C., Hannon, G. J., Wang, D.-Z. <strong>Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.</strong> Proc. Nat. Acad. Sci. 105: 2111-2116, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18256189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18256189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18256189[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0710228105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18256189">Chen et al. (2008)</a> concluded that DICER and miRNAs have critical roles in normal cardiac function and under pathologic conditions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18256189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Friedman, L. M., Dror, A. A., Mor, E., Tenne, T., Toren, G., Satoh, T., Biesemeier, D. J., Shomron, N., Fekete, D. M., Hornstein, E., Avraham, K. B. <strong>MicroRNAs are essential for development and function of inner ear hair cells in vertebrates.</strong> Proc. Nat. Acad. Sci. 106: 7915-7920, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416898</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416898[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0812446106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19416898">Friedman et al. (2009)</a> conditionally deleted Dicer in mouse inner ear sensory epithelium hair cells and in nonsensory supporting cells after their normal differentiation from progenitor cells. Removal of Dicer from sensory epithelium, which initially developed normally, caused abnormal growth and subsequent degeneration of mechanosensory hair cells, leading to deafness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19416898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a conditional deletion approach, <a href="#12" class="mim-tip-reference" title="Dugas, J. C., Cuellar, T. L., Scholze, A., Ason, B., Ibrahim, A., Emery, B., Zamanian, J. L., Foo, L. C., McManus, M. T., Barres, B. A. <strong>Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination.</strong> Neuron 65: 597-611, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223197[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2010.01.027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20223197">Dugas et al. (2010)</a> generated mice lacking Dicer in oligodendrocytes and oligodendrocyte precursor cells. These mice developed a shivering phenotype that was associated with defects in myelination. Microarray analysis identified Mir219 (see MIR219-1; <a href="/entry/611500">611500</a>), Mir138 (see MIR138-1; <a href="/entry/613394">613394</a>), and Mir338 (<a href="/entry/614059">614059</a>) as the most highly induced miRNAs during oligodendrocyte differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20223197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Independently, <a href="#65" class="mim-tip-reference" title="Zhao, X., He, X., Han, X., Yu, Y., Ye, F., Chen, Y., Hoang, T., Xu, X., Mi, Q.-S., Xin, M., Wang, F., Appel, B., Lu, Q. R. <strong>MicroRNA-mediated control of oligodendrocyte differentiation.</strong> Neuron 65: 612-626, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223198</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223198[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2010.02.018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20223198">Zhao et al. (2010)</a> created mice lacking Dicer in oligodendrocyte lineage cells. Mutant mice were obtained at a mendelian ratio, but they developed severe tremor and ataxia due to myelinating defects and died around postnatal week 3. Microarray analysis revealed significantly reduced Mir219 and Mir338 expression in both Dicer-knockout and Olig1 (<a href="/entry/606385">606385</a>)-knockout oligodendrocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20223198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Hebert, A. S., Papadopoulou, A. S., Smith, P., Galas, M.-C., Planel, E., Silahtaroglu, A. N., Sergeant, N., Buee, L., De Strooper, B. <strong>Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration.</strong> Hum. Molec. Genet. 19: 3959-3969, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20660113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20660113</a>] [<a href="https://doi.org/10.1093/hmg/ddq311" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20660113">Hebert et al. (2010)</a> showed that absence of Dicer in the adult mouse forebrain was accompanied by a mixed neurodegenerative phenotype. Although neuronal loss was observed in the hippocampus, cellular shrinkage was predominant in the cortex. Neuronal degeneration coincided with the hyperphosphorylation of endogenous tau (<a href="/entry/157140">157140</a>) at several epitopes associated with neurofibrillary pathology. Transcriptome analysis of enzymes involved in tau phosphorylation identified ERK1 (MAPK3; <a href="/entry/601795">601795</a>) as one of the candidate kinases responsible for this event in vivo. In addition, miRNAs belonging to the miR15 (<a href="/entry/609703">609703</a>) family were potent regulators of ERK1 expression in mouse neuronal cells and coexpressed with ERK1/2 in vivo. Finally, miR15a was specifically downregulated in Alzheimer disease (<a href="/entry/104300">104300</a>) brain. The authors hypothesized that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20660113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="allelicVariants" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<span href="#mimAllelicVariantsFold" id="mimAllelicVariantsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
|
|
</span>
|
|
<strong>14 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/606241" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606241[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
|
|
|
|
</div>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0001" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, LEU1583ARG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852976 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852976;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852976" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004725 OR RCV000240912" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004725, RCV000240912" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004725...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with 3 individuals affected with pleuropulmonary blastoma (PPB; <a href="/entry/601200">601200</a>) or lung cysts, <a href="#24" class="mim-tip-reference" title="Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J. <strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong> Science 325: 965 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556464</a>] [<a href="https://doi.org/10.1126/science.1174334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556464">Hill et al. (2009)</a> identified a heterozygous T-to-G transversion at nucleotide 4930 in exon 23 of the DICER1 gene, resulting in a leu-to-arg substitution at codon 1583 (L1583R). The mutation affected an evolutionarily conserved amino acid. The nonpolar-to-polar change was not a previously reported sequence variant, nor was it detected in 360 cancer-free controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0002" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, GLU493TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852977 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852977;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004726 OR RCV000240918 OR RCV000493893 OR RCV004719621" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004726, RCV000240918, RCV000493893, RCV004719621" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004726...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with 3 affected individuals, 1 with pleuropulmonary blastoma (PPB; <a href="/entry/601200">601200</a>), 1 with lung cysts, and 1 with cystic nephroma, <a href="#24" class="mim-tip-reference" title="Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J. <strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong> Science 325: 965 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556464</a>] [<a href="https://doi.org/10.1126/science.1174334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556464">Hill et al. (2009)</a> identified a heterozygous G-to-T transversion at nucleotide 1689 in exon 9 of DICER1, resulting in a glu-to-ter substitution at codon 493 (E493X). This mutation was associated with a reduced amount of mutant RNA and a loss of DICER1 staining in tumor-associated epithelium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0003" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, ARG934TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852978 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852978;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852978" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004727 OR RCV000240862 OR RCV000493701 OR RCV004719622" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004727, RCV000240862, RCV000493701, RCV004719622" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004727...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with pleuropulmonary blastoma (PPB; <a href="/entry/601200">601200</a>), <a href="#24" class="mim-tip-reference" title="Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J. <strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong> Science 325: 965 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556464</a>] [<a href="https://doi.org/10.1126/science.1174334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556464">Hill et al. (2009)</a> identified a heterozygous C-to-T transition at nucleotide 3012 in exon 18 of DICER1, resulting in an arg-to-ter substitution at codon 934 (R934X). Loss of DICER1 staining in tumor-associated epithelium was identified by immunohistochemistry. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0004" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, 1-BP INS, 2574A
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037690 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037690;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs886037690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs886037690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000240963 OR RCV000493145 OR RCV002282086" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000240963, RCV000493145, RCV002282086" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000240963...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with 2 affected individuals, 1 with pleuropulmonary blastoma (PPB; <a href="/entry/601200">601200</a>) and the other with lung cysts, <a href="#24" class="mim-tip-reference" title="Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J. <strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong> Science 325: 965 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556464</a>] [<a href="https://doi.org/10.1126/science.1174334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556464">Hill et al. (2009)</a> identified a heterozygous frameshift mutation resulting from insertion of an adenine at position 2574 in exon 15 of the DICER1 gene, resulting in a frameshift starting at codon 788 (T788Nfs). There was a reduced amount of mutant RNA from cell lines containing this mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0005" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, ARG534TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852979 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852979;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852979" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852979" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000004729 OR RCV000240896 OR RCV000851443 OR RCV004018561" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004729, RCV000240896, RCV000851443, RCV004018561" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004729...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with pleuropulmonary blastoma (PPB; <a href="/entry/601200">601200</a>), <a href="#24" class="mim-tip-reference" title="Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J. <strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong> Science 325: 965 only, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556464</a>] [<a href="https://doi.org/10.1126/science.1174334" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556464">Hill et al. (2009)</a> identified a heterozygous C-to-T transition at nucleotide 1812 in exon 10 of the DICER1 gene, resulting in an arg-to-ter substitution at codon 534 (R534X). This mutation was associated with loss of DICER1 staining in tumor-associated epithelium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0006" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GOITER, MULTINODULAR 1, WITH OR WITHOUT SERTOLI-LEYDIG CELL TUMORS, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, SER1826TER
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1595314576 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595314576;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1595314576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1595314576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023521 OR RCV000023522 OR RCV001201154" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023521, RCV000023522, RCV001201154" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023521...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with pleuropulmonary blastoma (PPB; <a href="/entry/601200">601200</a>) and cystic nephroma, <a href="#1" class="mim-tip-reference" title="Bahubeshi, A., Bal, N., Rio Frio, T., Hamel, N., Pouchet, C., Yilmaz, A., Bouron-Dal Soglio, D., Williams, G. M., Tischkowitz, M., Priest, J. R., Foulkes, W. D. <strong>Germline DICER1 mutations and familial cystic nephroma.</strong> J. Med. Genet. 47: 863-866, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21036787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21036787</a>] [<a href="https://doi.org/10.1136/jmg.2010.081216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21036787">Bahubeshi et al. (2010)</a> identified a heterozygous 5477C-A transversion in exon 25 of the DICER1 gene, resulting in a ser1826-to-ter (S1826X) substitution that would exclude the double-stranded RNA-binding domain. The patient died at age 5 years. Her brother, who also carried the mutation, had cystic nephroma without PPB and was alive at age 5 years. Heterozygosity for the mutation was also found in the mother, who had goiter (MNG1; <a href="/entry/138800">138800</a>) and in 2 unaffected sisters of the proband. There were 2 other maternal relatives with goiter, but DNA was not studied. In cystic nephroma tissue derived from the brother, there was no loss of heterozygosity at the DICER1 locus, but there was decreased immunostaining for the protein in renal tubules. The findings indicated that nephroma can be a part of the PPB spectrum and also illustrated that DICER1 mutations can predispose to goiter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21036787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0007" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 GOITER, MULTINODULAR 1, WITH OR WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, 4-BP DEL, 871AAAG
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1595447577 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595447577;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1595447577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1595447577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023523" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023523" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023523</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 members of a family with multinodular goiter with or without Sertoli-Leydig cell tumors (MNG1; <a href="/entry/138800">138800</a>), <a href="#52" class="mim-tip-reference" title="Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others. <strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong> J.A.M.A. 305: 68-77, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205968">Rio Frio et al. (2011)</a> identified a heterozygous 4-bp deletion (871delAAAG) in the DICER1 gene, resulting in a frameshift and premature termination. A mutant mRNA could not be detected due to nonsense-mediated mRNA decay. The family had originally been reported by <a href="#44" class="mim-tip-reference" title="O'Brien, P. K., Wilansky, D. L. <strong>Familial thyroid nodulation and arrhenoblastoma.</strong> Am. J. Clin. Path. 75: 578-581, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261577</a>] [<a href="https://doi.org/10.1093/ajcp/75.4.578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6261577">O'Brien and Wilansky (1981)</a>. The female proband had multinodular goiter at age 16 years and an ovarian Sertoli-Leydig cell tumor at age 18; 3 additional family members with the mutation had multinodular goiter only. Studies of the ovarian tumor showed no loss of heterozygosity for the DICER1 locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21205968+6261577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0008" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 GOITER, MULTINODULAR 1, WITH OR WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, 2457C-G
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1595380836 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595380836;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1595380836" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1595380836" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023525 OR RCV001201008" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023525, RCV001201008" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023525...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a family with multinodular goiter with or without Sertoli-Leydig cell tumors (MNG1; <a href="/entry/138800">138800</a>), <a href="#52" class="mim-tip-reference" title="Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others. <strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong> J.A.M.A. 305: 68-77, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205968">Rio Frio et al. (2011)</a> identified a heterozygous 2457C-G transversion in exon 16 of the DICER1 gene, resulting in a de novo splice site and an in-frame deletion of the first 21 bps of exon 16 (2437_2457del21). The mutant transcript generates a predicted DICER1 protein lacking amino acids ile813 to tyr819, resulting in an altered PAZ structure. The family had previously been reported by <a href="#43" class="mim-tip-reference" title="Niedziela, M. <strong>Virilizing ovarian tumor in a 14-year-old female with a prior familial multinodular goiter.</strong> Pediat. Blood Cancer 51: 543-545, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570301</a>] [<a href="https://doi.org/10.1002/pbc.21675" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18570301">Niedziela (2008)</a>. The proband developed multinodular goiter at age 9 years and an ovarian Sertoli-Leydig cell tumor at age 14. Two other family members developed multinodular goiter only at ages 12 and 17, respectively. There was no loss of heterozygosity at the DICER1 locus in tumor tissue, and immunohistochemical studies showed loss of protein staining in the goiter, intense staining in Sertoli cells, and weak staining in Leydig cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21205968+18570301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0009" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 GOITER, MULTINODULAR 1, WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER, SER839PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906934 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906934;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023526 OR RCV001201061 OR RCV002426517" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023526, RCV001201061, RCV002426517" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023526...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Canadian family with multinodular goiter without Sertoli-Leydig cell tumors (MNG1; <a href="/entry/138800">138800</a>) reported by <a href="#3" class="mim-tip-reference" title="Bignell, G. R., Canzian, F., Shayeghi, M., Stark, M., Shugart, Y. Y., Biggs, P., Mangion, J., Hamoudi, R., Rosenblatt, J., Buu, P., Sun, S., Stoffer, S. S., Goldgar, D. E., Romeo, G., Houlston, R. S., Narod, S. A., Stratton, M. R., Foulkes, W. D. <strong>Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.</strong> Am. J. Hum. Genet. 61: 1123-1130, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345104</a>] [<a href="https://doi.org/10.1086/301610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9345104">Bignell et al. (1997)</a>, <a href="#52" class="mim-tip-reference" title="Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others. <strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong> J.A.M.A. 305: 68-77, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205968">Rio Frio et al. (2011)</a> identified a heterozygous 2916C-T transition in the DICER1 gene, resulting in a ser839-to-phe (S839F) substitution in a highly conserved residue and predicted to disrupt an alpha-helix in the PAZ domain. The mutation was not found in 455 controls. The mutation was found in all 20 affected individuals and in none of 10 unaffected family members. There was no loss of heterozygosity at the DICER1 locus in tumor tissues analyzed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21205968+9345104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0010" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 GOITER, MULTINODULAR 1, WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, IVS17AS, G-T, -1
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1595374375 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595374375;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1595374375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1595374375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023524 OR RCV001201069" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023524, RCV001201069" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023524...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Canadian family with multinodular goiter (MNG1; <a href="/entry/138800">138800</a>) originally reported by <a href="#11" class="mim-tip-reference" title="Druker, H. A., Kasprzak, L., Begin, L. R., Jothy, S., Narod, S. A., Foulkes, W. D. <strong>Family with Graves disease, multinodular goiter, nonmedullary thyroid carcinoma, and alveolar rhabdomyosarcoma.</strong> Am. J. Med. Genet. 72: 30-33, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9295070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9295070</a>]" pmid="9295070">Druker et al. (1997)</a>, <a href="#52" class="mim-tip-reference" title="Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others. <strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong> J.A.M.A. 305: 68-77, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21205968">Rio Frio et al. (2011)</a> identified a heterozygous G-to-T transversion in intron 17 of the DICER1 gene, affecting a splice site and resulting in an in-frame deletion of exon 18, eliminating part of the PAZ domain. The mutation was not seen in 430 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=21205968+9295070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0011" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 RHABDOMYOSARCOMA, EMBRYONAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, 2-BP DEL, 3097CT
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037650 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037650;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs886037650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs886037650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056332 OR RCV001201022" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056332, RCV001201022" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056332...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which the proband had a cervical embryonal rhabdomyosarcoma (CERMS; see <a href="/entry/180295">180295</a>) and multinodular goiter (see <a href="/entry/138800">138800</a>), <a href="#14" class="mim-tip-reference" title="Foulkes, W. D., Bahubeshi, A., Hamel, N., Pasini, B., Asioli, S., Baynam, G., Choong, C. S., Charles, A., Frieder, R. P., Dishop, M. K., Graf, N., Ekim, M., Bouron-Dal Soglio, D., Arseneau, J., Young, R. H., Sabbaghian, N., Srivastava, A., Tischkowitz, M. D., Priest, J. R. <strong>Extending the phenotypes associated with DICER1 mutations.</strong> Hum. Mutat. 32: 1381-1384, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21882293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21882293</a>] [<a href="https://doi.org/10.1002/humu.21600" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21882293">Foulkes et al. (2011)</a> identified a heterozygous mutation in exon 21 of the DICER1 gene, a 2-basepair deletion (c.3907_3908delCT) that resulted in frameshift and premature termination (Leu1303ValfsTer4). Other mutation carriers in the family had multinodular goiter, lung cysts, esophageal hamartomatous polyp, and/or thyroid nodule. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21882293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0012" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 RHABDOMYOSARCOMA, EMBRYONAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, 6-BP DEL/1-BP INS, NT3611
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037651 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037651;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs886037651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs886037651" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056333 OR RCV001201011" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056333, RCV001201011" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056333...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which 2 members had cervical embryonal rhabdomyosarcoma (CERMS; see <a href="/entry/180295">180295</a>), <a href="#14" class="mim-tip-reference" title="Foulkes, W. D., Bahubeshi, A., Hamel, N., Pasini, B., Asioli, S., Baynam, G., Choong, C. S., Charles, A., Frieder, R. P., Dishop, M. K., Graf, N., Ekim, M., Bouron-Dal Soglio, D., Arseneau, J., Young, R. H., Sabbaghian, N., Srivastava, A., Tischkowitz, M. D., Priest, J. R. <strong>Extending the phenotypes associated with DICER1 mutations.</strong> Hum. Mutat. 32: 1381-1384, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21882293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21882293</a>] [<a href="https://doi.org/10.1002/humu.21600" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21882293">Foulkes et al. (2011)</a> identified a heterozygous indel mutation in exon 21 of the DICER1 gene (c.3611_3616delACTACAinsT) that resulted in frameshift and premature termination (Tyr1204LeufsTer29). The proband had lung cysts and multinodular goiter in addition to CERMS; other mutation carriers in the family had Sertoli-Leydig cell tumor, multinodular goiter, and pleomorphic sarcoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21882293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0013" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 GLOW SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, ASP1713VAL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1595331224 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595331224;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1595331224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1595331224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000735852 OR RCV000851425 OR RCV001201032" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000735852, RCV000851425, RCV001201032" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000735852...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with global developmental delay, lung cysts, overgrowth, and Wilms tumor (GLOW; <a href="/entry/618272">618272</a>), <a href="#30" class="mim-tip-reference" title="Klein, S., Lee, H., Ghahremani, S., Kempert, P., Ischander, M., Teitell, M. A., Nelson, S. F., Martinez-Agosto, J. A. <strong>Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome.</strong> J. Med. Genet. 51: 294-302, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24676357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24676357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24676357[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-101943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24676357">Klein et al. (2014)</a> identified a heterozygous A-to-T transversion at nucleotide 5138 of the DICER1 gene resulting in a valine substitution for the aspartic acid at codon 1713 (D1713V). Aspartic acid-1713 is highly conserved through evolution, and the mutation in this patient is 13 bp from the mutation in the second patient identified by the authors (<a href="#0014">606241.0014</a>), which occurred at a known metal binding site essential for DICER1 RNase IIIb domain function. The mutation was identified by whole-exome sequencing of DNA from peripheral mononuclear blood cells. The mutation occurred as a postzygotic event as it was absent from both parents and present in varying abundance in different tissues. <a href="#30" class="mim-tip-reference" title="Klein, S., Lee, H., Ghahremani, S., Kempert, P., Ischander, M., Teitell, M. A., Nelson, S. F., Martinez-Agosto, J. A. <strong>Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome.</strong> J. Med. Genet. 51: 294-302, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24676357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24676357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24676357[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-101943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24676357">Klein et al. (2014)</a> stated that the variant was absent from the EVS database and UCLA clinical genomics dataset. <a href="#21" class="mim-tip-reference" title="Hamosh, A. <strong>Personal Communication.</strong> Baltimore, Md. 12/30/2018."None>Hamosh (2018)</a> noted that the variant was not present in the gnomAD database (December 30, 2018). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24676357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div>
|
|
<a id="0014" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 GLOW SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
DICER1, ASP1709TYR
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1595331264 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595331264;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1595331264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1595331264" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000735853 OR RCV001200978" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000735853, RCV001200978" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000735853...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with global developmental delay, lung cysts, overgrowth, and Wilms tumor (GLOW; <a href="/entry/618272">618272</a>), <a href="#30" class="mim-tip-reference" title="Klein, S., Lee, H., Ghahremani, S., Kempert, P., Ischander, M., Teitell, M. A., Nelson, S. F., Martinez-Agosto, J. A. <strong>Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome.</strong> J. Med. Genet. 51: 294-302, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24676357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24676357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24676357[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1136/jmedgenet-2013-101943" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24676357">Klein et al. (2014)</a> identified a heterozygous G-to-T transversion at nucleotide 5125 of the DICER1 gene, resulting in an aspartic acid-to-tyrosine substitution at codon 1709 (D1709Y). The aspartic acid at position 1709 is highly conserved and functions as part of a metal binding site essential for 5-prime microRNA cleavage from mature pre-microRNAs and a hotspot for somatic mutations in cancers. <a href="#21" class="mim-tip-reference" title="Hamosh, A. <strong>Personal Communication.</strong> Baltimore, Md. 12/30/2018."None>Hamosh (2018)</a> noted that the variant was not present in the gnomAD database (December 30, 2018). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24676357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Bahubeshi2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bahubeshi, A., Bal, N., Rio Frio, T., Hamel, N., Pouchet, C., Yilmaz, A., Bouron-Dal Soglio, D., Williams, G. M., Tischkowitz, M., Priest, J. R., Foulkes, W. D.
|
|
<strong>Germline DICER1 mutations and familial cystic nephroma.</strong>
|
|
J. Med. Genet. 47: 863-866, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21036787/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21036787</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21036787" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2010.081216" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Bernstein2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bernstein, E., Kim, S. Y., Carmell, M. A., Murchison, E. P., Alcorn, H., Li, M. Z., Mills, A. A., Elledge, S. J., Anderson, K. V., Hannon, G. J.
|
|
<strong>Dicer is essential for mouse development.</strong>
|
|
Nature Genet. 35: 215-216, 2003. Note: Erratum: Nature Genet. 35: 287 only, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14528307/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14528307</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14528307" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1253" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bignell1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bignell, G. R., Canzian, F., Shayeghi, M., Stark, M., Shugart, Y. Y., Biggs, P., Mangion, J., Hamoudi, R., Rosenblatt, J., Buu, P., Sun, S., Stoffer, S. S., Goldgar, D. E., Romeo, G., Houlston, R. S., Narod, S. A., Stratton, M. R., Foulkes, W. D.
|
|
<strong>Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.</strong>
|
|
Am. J. Hum. Genet. 61: 1123-1130, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9345104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9345104</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9345104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/301610" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Blaszczyk2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Blaszczyk, J., Tropea, J. E., Bubunenenko, M., Routzahn, K. M., Waugh, D. S., Court, D. L., Ji, X.
|
|
<strong>Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage.</strong>
|
|
Structure 9: 1225-1236, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11738048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11738048</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11738048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0969-2126(01)00685-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Cheloufi2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., Hannon, G. J.
|
|
<strong>A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis.</strong>
|
|
Nature 465: 584-589, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20424607/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20424607</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20424607[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20424607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09092" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Chen2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chen, J.-F., Murchison, E. P., Tang, R., Callis, T. E., Tatsuguchi, M., Deng, Z., Rojas, M., Hammond, S. M., Schneider, M. D., Selzman, C. H., Meissner, G., Patterson, C., Hannon, G. J., Wang, D.-Z.
|
|
<strong>Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 2111-2116, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18256189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18256189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18256189[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18256189" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0710228105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Chendrimada2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R.
|
|
<strong>TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. (Letter)</strong>
|
|
Nature 436: 740-744, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15973356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15973356</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15973356[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15973356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature03868" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Cuellar2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cuellar, T. L., Davis, T. H., Nelson, P. T., Loeb, G. B., Harfe, B. D., Ullian, E., McManus, M. T.
|
|
<strong>Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 5614-5619, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18385371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18385371</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18385371[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18385371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0801689105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Czech2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Czech, B., Malone, C. D., Zhou, R., Stark, A., Schlingeheyde, C., Dus, M., Perrimon, N., Kellis, M., Wohlschlegel, J. A., Sachidanandam, R., Hannon, G. J., Brennecke, J.
|
|
<strong>An endogenous small interfering RNA pathway in Drosophila.</strong>
|
|
Nature 453: 798-802, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463631[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18463631" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature07007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Dias2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dias, C., Feng, J., Sun, H., Shao, N., Mazei-Robison, M. S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonte, B., Ribeiro, E., Liu, X., Kennedy, P., and 11 others.
|
|
<strong>Beta-catenin mediates stress resilience through Dicer1/microRNA regulation.</strong>
|
|
Nature 516: 51-55, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25383518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25383518</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25383518[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25383518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature13976" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Druker1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Druker, H. A., Kasprzak, L., Begin, L. R., Jothy, S., Narod, S. A., Foulkes, W. D.
|
|
<strong>Family with Graves disease, multinodular goiter, nonmedullary thyroid carcinoma, and alveolar rhabdomyosarcoma.</strong>
|
|
Am. J. Med. Genet. 72: 30-33, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9295070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9295070</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9295070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Dugas2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dugas, J. C., Cuellar, T. L., Scholze, A., Ason, B., Ibrahim, A., Emery, B., Zamanian, J. L., Foo, L. C., McManus, M. T., Barres, B. A.
|
|
<strong>Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination.</strong>
|
|
Neuron 65: 597-611, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223197</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223197[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20223197" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.neuron.2010.01.027" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Forman2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Forman, J. J., Legesse-Miller, A., Coller, H. A.
|
|
<strong>A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 14879-14884, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18812516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18812516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18812516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18812516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0803230105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Foulkes2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Foulkes, W. D., Bahubeshi, A., Hamel, N., Pasini, B., Asioli, S., Baynam, G., Choong, C. S., Charles, A., Frieder, R. P., Dishop, M. K., Graf, N., Ekim, M., Bouron-Dal Soglio, D., Arseneau, J., Young, R. H., Sabbaghian, N., Srivastava, A., Tischkowitz, M. D., Priest, J. R.
|
|
<strong>Extending the phenotypes associated with DICER1 mutations.</strong>
|
|
Hum. Mutat. 32: 1381-1384, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21882293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21882293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21882293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/humu.21600" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Francia2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Francia, S., Michelini, F., Saxena, A., Tang, D., de Hoon, M., Anelli, V., Mione, M., Carninci, P., d'Adda di Fagagna, F.
|
|
<strong>Site-specific DICER and DROSHA RNA products control the DNA-damage response.</strong>
|
|
Nature 488: 231-235, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22722852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22722852</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22722852[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22722852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature11179" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Friedman2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Friedman, L. M., Dror, A. A., Mor, E., Tenne, T., Toren, G., Satoh, T., Biesemeier, D. J., Shomron, N., Fekete, D. M., Hornstein, E., Avraham, K. B.
|
|
<strong>MicroRNAs are essential for development and function of inner ear hair cells in vertebrates.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 7915-7920, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19416898/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19416898</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19416898[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19416898" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0812446106" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Galiana-Arnoux2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Galiana-Arnoux, D., Dostert, C., Schneemann, A., Hoffmann, J. A., Imler, J.-L.
|
|
<strong>Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.</strong>
|
|
Nature Immun. 7: 590-597, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16554838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16554838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16554838" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ni1335" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Ghildiyal2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ghildiyal, M., Seitz, H., Horwich, M. D., Li, C., Du, T., Lee, S., Xu, J., Kittler, E. L. W., Zapp, M. L., Weng, Z., Zamore, P. D.
|
|
<strong>Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.</strong>
|
|
Science 320: 1077-1081, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18403677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18403677</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18403677[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18403677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1157396" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Giraldez2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Giraldez, A. J., Mishima, Y., Rihel, J., Grocock, R. J., Van Dongen, S., Inoue, K., Enright, A. J., Schier, A. F.
|
|
<strong>Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs.</strong>
|
|
Science 312: 75-79, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16484454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16484454</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16484454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1122689" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Gregory2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gregory, R. I., Chendrimada, T. P., Cooch, N., Shiekhattar, R.
|
|
<strong>Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.</strong>
|
|
Cell 123: 631-640, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16271387/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16271387</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16271387" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2005.10.022" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Hamosh2018" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hamosh, A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 12/30/2018.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Hatfield2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hatfield, S. D., Shcherbata, H. R., Fischer, K. A., Nakahara, K., Carthew, R. W., Ruohola-Baker, H.
|
|
<strong>Stem cell division is regulated by the microRNA pathway. (Letter)</strong>
|
|
Nature 435: 974-978, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature03816" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Hebert2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hebert, A. S., Papadopoulou, A. S., Smith, P., Galas, M.-C., Planel, E., Silahtaroglu, A. N., Sergeant, N., Buee, L., De Strooper, B.
|
|
<strong>Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration.</strong>
|
|
Hum. Molec. Genet. 19: 3959-3969, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20660113/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20660113</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20660113" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddq311" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Hill2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J.
|
|
<strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong>
|
|
Science 325: 965 only, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556464/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556464</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556464" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1174334" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Hutvagner2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hutvagner, G., McLachlan, J., Pasquinelli, A. E., Balint, E., Tuschl, T., Zamore, P. D.
|
|
<strong>A cellular function for the RNA-interference enzyme dicer in the maturation of the let-7 small temporal RNA.</strong>
|
|
Science 293: 834-838, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11452083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11452083</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11452083" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1062961" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Jing2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.-C., Gram, H., Han, J.
|
|
<strong>Involvement of microRNA in AU-rich element-mediated mRNA instability.</strong>
|
|
Cell 120: 623-634, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15766526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15766526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15766526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2004.12.038" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Kaneko2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., Kleinman, M. E., Ponicsan, S. L., Hauswirth, W. W., Chiodo, V. A., Kariko, K., Yoo, J. W., and 30 others.
|
|
<strong>DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration.</strong>
|
|
Nature 471: 325-330, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21297615/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21297615</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21297615[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21297615" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09830" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Kanellopoulou2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kanellopoulou, C., Muljo, S. A., Kung, A. L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D. M., Rajewsky, K.
|
|
<strong>Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing.</strong>
|
|
Genes Dev. 19: 489-501, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15713842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15713842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15713842[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15713842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.1248505" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Kawamura2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kawamura, Y., Saito, K., Kin, T., Ono, Y., Asai, K., Sunohara, T., Okada, T. N., Siomi, M. C., Siomi, H.
|
|
<strong>Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells.</strong>
|
|
Nature 453: 793-797, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463636</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18463636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature06938" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Klein2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Klein, S., Lee, H., Ghahremani, S., Kempert, P., Ischander, M., Teitell, M. A., Nelson, S. F., Martinez-Agosto, J. A.
|
|
<strong>Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome.</strong>
|
|
J. Med. Genet. 51: 294-302, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24676357/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24676357</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24676357[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24676357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2013-101943" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Kobayashi2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kobayashi, T., Lu, J., Cobb, B. S., Rodda, S. J., McMahon, A. P., Schipani, E., Merkenschlager, M., Kronenberg, H. M.
|
|
<strong>Dicer-dependent pathways regulate chondrocyte proliferation and differentiation.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 1949-1954, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18238902/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18238902</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18238902[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18238902" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0707900105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Koralov2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Koralov, S. B., Muljo, S. A., Galler, G. R., Krek, A., Chakraborty, T., Kanellopoulou, C., Jensen, K., Cobb, B. S., Merkenschlager, M., Rajewsky, N., Rajewsky, K.
|
|
<strong>Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage.</strong>
|
|
Cell 132: 860-874, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18329371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18329371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18329371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2008.02.020" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Li2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, Y., Lu, J., Han, Y., Fan, X., Ding, S.-W.
|
|
<strong>RNA interference functions as an antiviral immunity mechanism in mammals.</strong>
|
|
Science 342: 231-234, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24115437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24115437</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24115437[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24115437" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1241911" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="MacRae2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
MacRae, I. J., Zhou, K., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., Adams, P. D., Doudna, J. A.
|
|
<strong>Structural basis for double-stranded RNA processing by Dicer.</strong>
|
|
Science 311: 195-198, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16410517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16410517</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16410517" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1121638" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Maillard2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maillard, P. V., Ciaudo, C., Marchais, A., Li, Y., Jay, F., Ding, S. W., Voinnet, O.
|
|
<strong>Antiviral RNA interference in mammalian cells.</strong>
|
|
Science 342: 235-238, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24115438/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24115438</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24115438[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24115438" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1241930" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Maniataki2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Maniataki, E., Mourelatos, Z.
|
|
<strong>A human, ATP-independent, RISC assembly machine fueled by pre-miRNA.</strong>
|
|
Genes Dev. 19: 2979-2990, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16357216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16357216</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16357216[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16357216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.1384005" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Matsuda2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Matsuda, S., Ichigotani, Y., Okuda, T., Irimura, T., Nakatsugawa, S., Hamaguchi, M.
|
|
<strong>Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.</strong>
|
|
Biochim. Biophys. Acta 1490: 163-169, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10786632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10786632</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10786632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0167-4781(99)00221-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Merritt2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Merritt, W. M., Lin, Y. G., Han, L. Y., Kamat, A. A., Spannuth, W. A., Schmandt, R., Urbauer, D., Pennacchio, L. A., Cheng, J.-F., Nick, A. M., Deavers, M. T., Mourad-Zeidan, A., and 10 others.
|
|
<strong>Dicer, Drosha, and outcomes in patients with ovarian cancer.</strong>
|
|
New Eng. J. Med. 359: 2641-2650, 2008. Note: Erratum: New Eng. J. Med. 363: 1877 only, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19092150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19092150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19092150[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19092150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa0803785" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Merritt2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Merritt, W. M., Urbauer, D. L., Sood, A. K.
|
|
<strong>Reply to Kobel et al. (Letter)</strong>
|
|
New Eng. J. Med. 360: 1151 only, 2009.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Muljo2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Muljo, S. A., Ansel, K. M., Kanellopoulou, C., Livingston, D. M., Rao, A., Rajewsky, K.
|
|
<strong>Aberrant T cell differentiation in the absence of Dicer.</strong>
|
|
J. Exp. Med. 202: 261-269, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16009718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16009718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16009718[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16009718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1084/jem.20050678" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Murchison2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Murchison, E. P., Stein, P., Xuan, Z., Pan, H., Zhang, M. Q., Schultz, R. M., Hannon, G. J.
|
|
<strong>Critical roles for Dicer in the female germline.</strong>
|
|
Genes Dev. 21: 682-693, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17369401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17369401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17369401[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17369401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.1521307" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Nakagawa2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nakagawa, A., Shi, Y., Kage-Nakadai, E., Mitani, S., Xue, D.
|
|
<strong>Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease.</strong>
|
|
Science 328: 327-334, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223951</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223951[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20223951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1182374" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Niedziela2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Niedziela, M.
|
|
<strong>Virilizing ovarian tumor in a 14-year-old female with a prior familial multinodular goiter.</strong>
|
|
Pediat. Blood Cancer 51: 543-545, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18570301/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18570301</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18570301" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/pbc.21675" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="O'Brien1981" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
O'Brien, P. K., Wilansky, D. L.
|
|
<strong>Familial thyroid nodulation and arrhenoblastoma.</strong>
|
|
Am. J. Clin. Path. 75: 578-581, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6261577/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6261577</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6261577" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/ajcp/75.4.578" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Okamura2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Okamura, K., Chung, W.-J., Ruby, J. G., Guo, H., Bartel, D. P., Lai, E. C.
|
|
<strong>The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs.</strong>
|
|
Nature 453: 803-806, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18463630/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18463630</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18463630[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18463630" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature07015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Otsuka2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Otsuka, M., Jing, Q., Georgel, P., New, L., Chen, J., Mols, J., Kang, Y. J., Jiang, Z., Du, X., Cook, R., Das, S. C., Pattnaik, A. K., Beutler, B., Han, J.
|
|
<strong>Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression.</strong>
|
|
Immunity 27: 123-134, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17613256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17613256</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17613256" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.immuni.2007.05.014" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="Palculict2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Palculict, T. B., Ruteshouser, E. C., Fan, Y., Wang, W., Strong, L., Huff, V.
|
|
<strong>Identification of germline DICER1 mutations and loss of heterozygosity in familial Wilms tumour.</strong>
|
|
J. Med. Genet. 53: 385-388, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26566882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26566882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26566882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26566882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2015-103311" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Park2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Park, J.-E., Heo, I., Tian, Y., Simanshu, D. K., Chang, H., Jee, D., Patel, D. J., Kim, V. N.
|
|
<strong>Dicer recognizes the 5-prime end of RNA for efficient and accurate processing.</strong>
|
|
Nature 475: 201-205, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21753850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21753850</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21753850[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21753850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature10198" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Provost1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Provost, P., Samuelsson, B., Radmark, O.
|
|
<strong>Interaction of 5-lipoxygenase with cellular proteins.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 1881-1885, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10051563/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10051563</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10051563[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10051563" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.96.5.1881" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="50" class="mim-anchor"></a>
|
|
<a id="Raaijmakers2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T.
|
|
<strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong>
|
|
Nature 464: 852-857, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20305640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20305640</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20305640[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20305640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature08851" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="51" class="mim-anchor"></a>
|
|
<a id="Rakheja2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rakheja, D., Chen, K. S., Liu, Y., Shukla, A. A., Schmid, V., Chang, T.-C., Khokhar, S., Wickiser, J. E., Karandikar, N. J., Malter, J. S., Mendell, J. T., Amatruda, J. F.
|
|
<strong>Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours.</strong>
|
|
Nature Commun. 5: 4802, 2014. Note: Electronic Article. Erratum: Nature Commun. 8: 16177, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25190313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25190313</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25190313[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25190313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ncomms5802" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="52" class="mim-anchor"></a>
|
|
<a id="Rio Frio2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others.
|
|
<strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong>
|
|
J.A.M.A. 305: 68-77, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21205968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21205968</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21205968[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21205968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/jama.2010.1910" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="53" class="mim-anchor"></a>
|
|
<a id="Sabbaghian2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Sabbaghian, N., Hamel, N., Srivastava, A., Albrecht, S., Priest, J. R., Foulkes, W. D.
|
|
<strong>Germline DICER1 mutation and associated loss of heterozygosity in a pineoblastoma.</strong>
|
|
J. Med. Genet. 49: 417-419, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22717647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22717647</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22717647" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2012-100898" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="54" class="mim-anchor"></a>
|
|
<a id="Su2010" class="mim-anchor"></a>
|
|
<div class="mim-changed mim-change">
|
|
<p class="mim-text-font">
|
|
Su, X., Chakravarti, D., Cho, M. S., Liu, L., Gi, Y. J., Lin, Y.-L., Leung, M. L., El-Naggar, A., Creighton, C. J., Suraokar, M. B., Wistuba, I., Flores, E. R.
|
|
<strong>TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs.</strong>
|
|
Nature 467: 986-990, 2010. Note: Erratum: Nature 632: E2, 2024.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20962848/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20962848</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20962848[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20962848" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09459" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="55" class="mim-anchor"></a>
|
|
<a id="Tam2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tam, O. H., Aravin, A. A., Stein, P., Girard, A., Murchison, E. P., Cheloufi, S., Hodges, E., Anger, M., Sachidanandam, R., Schultz, R. M., Hannon, G. J.
|
|
<strong>Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.</strong>
|
|
Nature 453: 534-538, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404147</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18404147[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18404147" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature06904" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="56" class="mim-anchor"></a>
|
|
<a id="Tarallo2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., Albuquerque, R. J. C., Hauswirth, W. W., and 17 others.
|
|
<strong>DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88.</strong>
|
|
Cell 149: 847-859, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22541070/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22541070</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22541070[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22541070" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2012.03.036" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="57" class="mim-anchor"></a>
|
|
<a id="Tomari2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tomari, Y., Matranga, C., Haley, B., Martinez, N., Zamore, P. D.
|
|
<strong>A protein sensor for siRNA asymmetry.</strong>
|
|
Science 306: 1377-1380, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15550672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15550672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15550672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1102755" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="58" class="mim-anchor"></a>
|
|
<a id="Volpe2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Volpe, T. A., Kidner, C., Hall, I. M., Teng, G., Grewal, S. I. S., Martienssen, R. A.
|
|
<strong>Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi.</strong>
|
|
Science 297: 1833-1837, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12193640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12193640</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12193640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1074973" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="59" class="mim-anchor"></a>
|
|
<a id="Wang2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, X.-H., Aliyari, R., Li, W.-X., Li, H.-W., Kim, K., Carthew, R., Atkinson, P., Ding, S.-W.
|
|
<strong>RNA interference directs innate immunity against viruses in adult Drosophila.</strong>
|
|
Science 312: 452-454, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16556799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16556799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16556799[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16556799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1125694" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="60" class="mim-anchor"></a>
|
|
<a id="Watanabe2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi-Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., Surani, M. A., Sakaki, Y., Sasaki, H.
|
|
<strong>Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.</strong>
|
|
Nature 453: 539-543, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18404146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18404146</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18404146" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature06908" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="61" class="mim-anchor"></a>
|
|
<a id="Wienholds2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wienholds, E., Koudijs, M. J., van Eeden, F. J. M., Cuppen, E., Plasterk, R. H. A.
|
|
<strong>The microRNA-producing enzyme Dicer1 is essential for zebrafish development.</strong>
|
|
Nature Genet. 35: 217-218, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14528306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14528306</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14528306" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1251" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="62" class="mim-anchor"></a>
|
|
<a id="Yi2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yi, R., O'Carroll, D., Pasolli, H. A., Zhang, Z., Dietrich, F. S., Tarakhovsky, A., Fuchs, E.
|
|
<strong>Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs.</strong>
|
|
Nature Genet. 38: 356-362, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16462742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16462742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16462742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1744" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="63" class="mim-anchor"></a>
|
|
<a id="Zhang2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E., Filipowicz, W.
|
|
<strong>Single processing center models for human Dicer and bacterial RNase III.</strong>
|
|
Cell 118: 57-68, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15242644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15242644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15242644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2004.06.017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="64" class="mim-anchor"></a>
|
|
<a id="Zhang2006" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhang, L., Huang, J., Yang, N., Greshock, J., Megraw, M. S., Giannakakis, A., Liang, S., Naylor, T. L., Barchetti, A., Ward, M. R., Yao, G., Medina, A., O'Brien-Jenkins, A., Katsaros, D., Hatzigeorgiou, A., Gimotty, P. A., Weber, B. L., Coukos, G.
|
|
<strong>MicroRNAs exhibit high frequency genomic alterations in human cancer.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 9136-9141, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16754881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16754881</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16754881[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16754881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0508889103" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="65" class="mim-anchor"></a>
|
|
<a id="Zhao2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhao, X., He, X., Han, X., Yu, Y., Ye, F., Chen, Y., Hoang, T., Xu, X., Mi, Q.-S., Xin, M., Wang, F., Appel, B., Lu, Q. R.
|
|
<strong>MicroRNA-mediated control of oligodendrocyte differentiation.</strong>
|
|
Neuron 65: 612-626, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223198</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223198[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20223198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.neuron.2010.02.018" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="66" class="mim-anchor"></a>
|
|
<a id="Zhao2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Zhao, Y., Ransom, J. F., Li, A., Vedantham, V., von Drehle, M., Muth, A. N., Tsuchihashi, T., McManus, M. T., Schwartz, R. J., Srivastava, D.
|
|
<strong>Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.</strong>
|
|
Cell 129: 303-317, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17397913/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17397913</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17397913" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cell.2007.03.030" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 01/04/2019
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 11/08/2017<br>George E. Tiller - updated : 06/21/2017<br>Ada Hamosh - updated : 1/14/2015<br>Ada Hamosh - updated : 11/24/2014<br>Ada Hamosh - updated : 1/31/2014<br>Ada Hamosh - updated : 12/6/2013<br>Ada Hamosh - updated : 10/10/2013<br>Paul J. Converse - updated : 3/13/2013<br>Paul J. Converse - updated : 10/23/2012<br>Ada Hamosh - updated : 8/28/2012<br>Cassandra L. Kniffin - updated : 4/2/2012<br>Ada Hamosh - updated : 8/24/2011<br>Patricia A. Hartz - updated : 6/14/2011<br>Ada Hamosh - updated : 6/7/2011<br>Cassandra L. Kniffin - updated : 3/16/2011<br>Ada Hamosh - updated : 12/27/2010<br>Patricia A. Hartz - updated : 8/20/2010<br>Ada Hamosh - updated : 6/14/2010<br>Ada Hamosh - updated : 5/26/2010<br>Ada Hamosh - updated : 5/10/2010<br>Marla J. F. O'Neill - updated : 12/9/2009<br>Ada Hamosh - updated : 9/9/2009<br>Patricia A. Hartz - updated : 8/20/2009<br>Patricia A. Hartz - updated : 5/5/2009<br>Cassandra L. Kniffin - updated : 3/19/2009<br>Paul J. Converse - updated : 2/6/2009<br>Cassandra L. Kniffin - updated : 1/30/2009<br>Patricia A. Hartz - updated : 8/18/2008<br>Ada Hamosh - updated : 7/9/2008<br>Ada Hamosh - updated : 6/11/2008<br>Ada Hamosh - updated : 6/10/2008<br>Cassandra L. Kniffin - updated : 4/28/2008<br>Paul J. Converse - updated : 10/24/2007<br>Patricia A. Hartz - updated : 5/2/2007<br>Paul J. Converse - updated : 12/6/2006<br>Patricia A. Hartz - updated : 7/28/2006<br>Ada Hamosh - updated : 5/15/2006<br>Ada Hamosh - updated : 4/25/2006<br>Ada Hamosh - updated : 4/18/2006<br>Paul J. Converse - updated : 4/3/2006<br>Victor A. McKusick - updated : 3/6/2006<br>Patricia A. Hartz - updated : 2/10/2006<br>Ada Hamosh - updated : 9/7/2005<br>Stylianos E. Antonarakis - updated : 3/28/2005<br>Patricia A. Hartz - updated : 3/8/2005<br>Ada Hamosh - updated : 12/10/2004<br>Stylianos E. Antonarakis - updated : 8/3/2004<br>Victor A. McKusick - updated : 10/9/2003<br>Ada Hamosh - updated : 11/20/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 8/31/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 01/15/2025
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 10/08/2019<br>carol : 08/26/2019<br>carol : 01/08/2019<br>alopez : 01/04/2019<br>alopez : 01/04/2019<br>alopez : 04/09/2018<br>carol : 01/17/2018<br>carol : 11/14/2017<br>carol : 11/13/2017<br>carol : 11/10/2017<br>ckniffin : 11/08/2017<br>alopez : 06/21/2017<br>alopez : 06/21/2017<br>joanna : 10/16/2016<br>carol : 10/05/2016<br>alopez : 10/02/2015<br>carol : 5/7/2015<br>alopez : 1/14/2015<br>alopez : 11/24/2014<br>alopez : 1/31/2014<br>alopez : 12/6/2013<br>alopez : 10/10/2013<br>alopez : 10/10/2013<br>carol : 9/16/2013<br>terry : 4/4/2013<br>mgross : 3/18/2013<br>mgross : 3/18/2013<br>terry : 3/13/2013<br>mgross : 2/5/2013<br>mgross : 11/21/2012<br>terry : 10/23/2012<br>alopez : 8/30/2012<br>terry : 8/28/2012<br>carol : 6/4/2012<br>carol : 4/4/2012<br>ckniffin : 4/2/2012<br>alopez : 8/25/2011<br>terry : 8/24/2011<br>mgross : 6/22/2011<br>terry : 6/14/2011<br>alopez : 6/14/2011<br>alopez : 6/14/2011<br>terry : 6/7/2011<br>terry : 3/25/2011<br>terry : 3/18/2011<br>terry : 3/18/2011<br>wwang : 3/17/2011<br>ckniffin : 3/16/2011<br>alopez : 1/5/2011<br>terry : 12/27/2010<br>mgross : 9/1/2010<br>terry : 8/20/2010<br>alopez : 6/21/2010<br>terry : 6/14/2010<br>alopez : 5/27/2010<br>alopez : 5/27/2010<br>terry : 5/26/2010<br>alopez : 5/10/2010<br>wwang : 12/11/2009<br>terry : 12/9/2009<br>alopez : 9/10/2009<br>terry : 9/9/2009<br>mgross : 8/25/2009<br>terry : 8/20/2009<br>mgross : 5/5/2009<br>wwang : 3/20/2009<br>ckniffin : 3/19/2009<br>mgross : 2/6/2009<br>mgross : 2/6/2009<br>carol : 2/6/2009<br>ckniffin : 1/30/2009<br>wwang : 10/6/2008<br>wwang : 8/22/2008<br>terry : 8/18/2008<br>wwang : 7/15/2008<br>terry : 7/9/2008<br>alopez : 6/11/2008<br>terry : 6/10/2008<br>wwang : 6/6/2008<br>ckniffin : 4/28/2008<br>mgross : 10/24/2007<br>wwang : 5/2/2007<br>wwang : 5/2/2007<br>mgross : 12/6/2006<br>wwang : 8/7/2006<br>terry : 7/28/2006<br>alopez : 5/23/2006<br>terry : 5/15/2006<br>alopez : 4/25/2006<br>terry : 4/25/2006<br>alopez : 4/21/2006<br>terry : 4/18/2006<br>mgross : 4/5/2006<br>terry : 4/3/2006<br>wwang : 3/29/2006<br>terry : 3/24/2006<br>alopez : 3/9/2006<br>terry : 3/6/2006<br>mgross : 3/1/2006<br>wwang : 2/10/2006<br>alopez : 9/14/2005<br>terry : 9/7/2005<br>mgross : 3/28/2005<br>mgross : 3/8/2005<br>alopez : 12/15/2004<br>terry : 12/10/2004<br>mgross : 8/3/2004<br>alopez : 1/16/2004<br>alopez : 10/31/2003<br>alopez : 10/14/2003<br>alopez : 10/13/2003<br>terry : 10/9/2003<br>cwells : 11/20/2002<br>terry : 11/18/2002<br>alopez : 8/31/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 606241
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
DICER 1, RIBONUCLEASE III; DICER1
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
DICER, DROSOPHILA, HOMOLOG OF, 1<br />
|
|
DCR1<br />
|
|
HELICASE WITH RNASE MOTIF; HERNA<br />
|
|
HELICASE-MOI<br />
|
|
K12H4.8-LIKE<br />
|
|
KIAA0928
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: DICER1</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 702411003, 782722002;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 14q32.13
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 14:95,086,228-95,158,010 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
14q32.13
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
GLOW syndrome, somatic mosaic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
618272
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
138800
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Pleuropulmonary blastoma
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601200
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Rhabdomyosarcoma, embryonal, 2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
180295
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The DICER1 gene, a member of the ribonuclease III (RNaseIII) family, is involved in the generation of microRNAs (miRNAs), which modulate gene expression at the posttranscriptional level (summary by Rio Frio et al., 2011). DICER1 possesses an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus DICER, also known as helicase-MOI, is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression (Matsuda et al., 2000). </p><p>Evidence also suggests that DICER1 may act as a haploinsufficient tumor suppressor gene (Bahubeshi et al., 2010; Rio Frio et al., 2011). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>To identify proteins interacting with 5-lipoxygenase (ALOX5; 152390), Provost et al. (1999) used a yeast 2-hybrid approach to screen a human lung cDNA library. A 2.1-kb clone contained a partial cDNA of a human protein with high homology to the hypothetical helicase K12H4.8 from C. elegans. Analysis of the predicted amino acid sequence revealed the presence of an RNase III motif and a double-stranded RNA (dsRNA)-binding domain, indicative of a protein of nuclear origin. C. elegans K12H4.8 and the human homolog share 58% identity over 275 amino acids. </p><p>Matsuda et al. (2000) isolated a full-length cDNA encoding a gene they called HERNA for 'helicase with RNase motif.' The HERNA cDNA consists of 7,037 basepairs and has a predicted open reading frame encoding 1,924 amino acids. Matsuda et al. (2000) also recognized the homology to C. elegans K12H4.8. HERNA expression was detected by cycle-limited RT-PCR in brain, heart, lung, liver, pancreas, kidney, and placenta, but not in skeletal muscle, suggesting that HERNA may be ubiquitously expressed at variable levels. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Matsuda et al. (2000) used PCR-based monochromosomal somatic cell hybrid mapping to localize the HERNA gene to human chromosome 14. Analysis of radiation hybrid mapping panels refined the localization to 14q31. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
MacRae et al. (2006) determined the crystal structure of DICER. In an intact DICER enzyme, the PAZ domain, a module that binds the end of dsRNA, is separated from the 2 catalytic RNase III domains by a flat, positively charged surface. The 65-angstrom distance between the PAZ and RNase III domains matches the length spanned by 25 basepairs of RNA. Thus, MacRae et al. (2006) concluded that Dicer itself is a molecular ruler that recognizes dsRNA and cleaves a specified distance from the helical end. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The 21-nucleotide small temporal RNA (stRNA) let7 (605386) regulates developmental timing in C. elegans and probably in other bilateral animals. Hutvagner et al. (2001) presented in vivo and in vitro evidence that in Drosophila, a developmentally regulated precursor RNA is cleaved by an RNA interference-like mechanism to produce mature let7 stRNA. Targeted disruption in cultured human cells of the mRNA encoding the enzyme DICER, which acts in the RNA interference pathway, leads to accumulation of the LET7 precursor. Thus, Hutvagner et al. (2001) concluded that the RNA interference and stRNA pathways intersect. Both pathways require the RNA processing enzyme DICER to produce the active small RNA component that represses gene expression. </p><p>In S. pombe, Volpe et al. (2002) deleted the argonaute (AGO1, or EIF2C1; 606228), DICER, and RNA-dependent RNA polymerase gene homologs, which encode part of the machinery responsible for RNA interference. Deletion resulted in the aberrant accumulation of complementary transcripts from centromeric heterochromatic repeats. This was accompanied by transcription of derepression of transgenes integrated at the centromere, loss of histone H3 (see 602810) lysine-9 methylation, and impairment of centromere function. Volpe et al. (2002) proposed that double-stranded RNA arising from centromeric repeats targets formation and maintenance of heterochromatin through RNA interference. </p><p>DICER contains 2 domains related to the bacterial double-stranded RNA (dsRNA)-specific endonuclease, RNase III, which functions as a homodimer. Based on an x-ray structure of the Aquifex aeolicus RNase III, Blaszczyk et al. (2001) proposed models of the enzyme interaction with dsRNA and its cleavage at 2 composite catalytic centers. Zhang et al. (2004) generated mutations in human DICER and E. coli RNase III residues implicated in the catalysis and studied their effects on RNA processing. They determined that both enzymes have only 1 processing center that contains 2 RNA cleavage sites and generates products with 2-nucleotide 3-prime overhangs. Zhang et al. (2004) proposed that DICER functions through intramolecular dimerization of its 2 RNase III domains, assisted by the flanking RNA-binding domains, PAZ and dsRBD. </p><p>Tomari et al. (2004) showed that in Drosophila, the orientation of the DICER2/R2D2 protein heterodimer on the small interfering RNA (siRNA) duplex determines which siRNA strand associates with the core RNA-induced silencing complex (RISC) protein Argonaute-2 (AGO2, or EIF2C2; 606229). R2D2 binds the siRNA end with the greatest double-stranded character, thereby orienting the heterodimer on the siRNA duplex. Strong R2D2 binding requires a 5-prime-phosphate on the siRNA strand that is excluded from the RISC. Thus, Tomari et al. (2004) concluded that R2D2 is both a protein sensor for siRNA thermodynamic asymmetry and a licensing factor for entry of authentic siRNAs into the RNAi pathway. </p><p>AU-rich elements (AREs) in the 3-prime UTRs of unstable mRNAs dictate their degradation. Using an RNA interference-based screen in Drosophila S2 cells, Jing et al. (2005) found that Dicer-1, Ago1, and Ago2, components involved in microRNA (miRNA) processing and function, were required for rapid decay of mRNA containing AREs of tumor necrosis factor-alpha (TNF; 191160). The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. Jing et al. (2005) showed that miRNA16 (miR16), a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, was required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay was sequence-specific and required the ARE-binding protein tristetraprolin (TTP, or ZFP36; 190700). TTP did not directly bind miR16, but interacted through association with Ago/EIF2C family members to complex with miR16 and assist in the targeting of ARE. Jing et al. (2005) concluded that miRNA targeting of ARE appears to be an essential step in ARE-mediated mRNA degradation. </p><p>Chendrimada et al. (2005) demonstrated that TRBP (605053), which contains 3 double-stranded RNA-binding domains, is an integral component of a Dicer-containing complex. Biochemical analysis of TRBP-containing complexes revealed the association of Dicer-TRBP with AGO2, the catalytic engine of RISC. The physical association of Dicer-TRBP and AGO2 was confirmed after the isolation of the ternary complex using Flag-tagged AGO2 cell lines. In vitro reconstitution assays demonstrated that TRBP is required for the recruitment of AGO2 to the small interfering RNA (siRNA) bound by Dicer. Knockdown of TRBP resulted in destabilization of Dicer and a consequent loss of miRNA biogenesis. Finally, depletion of the Dicer-TRBP complex via exogenously introduced siRNAs diminished RISC-mediated reporter gene silencing. Chendrimada et al. (2005) concluded that these results support a role of the Dicer-TRBP complex not only in miRNA processing but also as a platform for RISC assembly. </p><p>Hatfield et al. (2005) reported the necessity of the miRNA pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell markers and genetic interactions, Hatfield et al. (2005) concluded that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. </p><p>Maniataki and Mourelatos (2005) found that pre-miRNA-fueled assembly of RISC in humans differed from the assembly of RISC by siRNA in Drosophila in terms of the sequence of events, energy requirements, and the final RISC product. In human cells, DICER was associated with AGO2 prior to its encounter with pre-miRNA. The preformed AGO2/DICER-containing complex assembled RISCs from pre-miRNAs but not from siRNA duplexes, and the process was independent of added ATP or GTP. The final RISC product, a ribonucleoprotein made up of AGO2 and miRNA, could be released from DICER. </p><p>Gregory et al. (2005) immunoprecipitated approximately 500-kD RISC complexes from human embryonic kidney cells and found that they contained DICER, TRBP, and AGO2. The RISC complex cleaved target RNA using pre-miRNA hairpin as well as duplex siRNA, but it displayed nearly 10-fold greater activity using the pre-miRNA DICER substrate. RISC distinguished the guide strand of the siRNA from the passenger strand and specifically incorporated the guide strand. ATP was not required for miRNA processing, RISC assembly, or multiple rounds of AGO2-mediated target RNA cleavage. </p><p>Giraldez et al. (2006) found that zebrafish embryos deficient for maternal and zygotic Dicer activity cannot generate mature miRNAs. These mutants displayed defects during gastrulation and brain morphogenesis that were rescued by injection of processed miRNAs belonging to the miR430 family (homologous to human miR302A, 614596). Giraldez et al. (2006) used a microarray approach and in vivo target validation to determine that miR430 regulates several hundred target mRNA molecules in the zebrafish zygote and embryo. Most targets are maternally expressed mRNAs that accumulate in the absence of miR430. Giraldez et al. (2006) also showed that miR430 accelerated the deadenylation of target mRNAs. They concluded that miR430 facilitates the deadenylation and clearance of maternal mRNAs during early embryogenesis. </p><p>Tam et al. (2008) showed that a subset of pseudogenes generates endogenous small interfering RNAs (endo-siRNAs) in mouse oocytes. These endo-siRNAs are often processed from double-stranded RNAs formed by hybridization of spliced transcripts from protein-coding genes to antisense transcripts from homologous pseudogenes. An inverted repeat pseudogene can also generate abundant small RNAs directly. A second class of endo-siRNAs may enforce repression of mobile genetic elements, acting together with Piwi-interacting RNAs. Loss of Dicer, a protein integral to small RNA production, increases expression of endo-siRNA targets, demonstrating their regulatory activity. Tam et al. (2008) concluded that their findings indicated a function for pseudogenes in regulating gene expression by means of the RNA interference pathway and may, in part, explain the evolutionary pressure to conserve argonaute (see 607355)-mediated catalysis in humans. </p><p>Using mouse oocytes, Watanabe et al. (2008) demonstrated that endogenous siRNAs are derived from naturally occurring double-stranded RNAs (dsRNAs) and have roles in the regulation of gene expression. By means of deep sequencing, Watanabe et al. (2008) identified a large number of both approximately 25- to 27-nucleotide Piwi-interacting RNAs (piRNAs) and approximately 21-nucleotide siRNAs corresponding to mRNAs or retrotransposons in growing oocytes. piRNAs are bound to Mili (610310) and have a role in the regulation of retrotransposons. siRNAs are exclusively mapped to retrotransposons or other genomic regions that produce transcripts capable of forming double-stranded RNA structures. Inverted repeat structures, bidirectional transcription, and antisense transcripts from various loci are sources of the double-stranded RNAs. Some precursor transcripts of siRNAs are derived from expressed pseudogenes, indicating that one role of pseudogenes is to adjust the level of the founding source mRNA through RNAi. Watanabe et al. (2008) showed that loss of Dicer or Ago2 (606229) resulted in decreased levels of siRNAs and increased levels of retrotransposon and protein-coding transcripts complementary to the siRNAs. Thus, Watanabe et al. (2008) concluded that the RNA interference (RNAi) pathway regulates both protein-coding transcripts and retrotransposons in mouse oocytes. They also concluded that their results revealed a role for endogenous siRNAs in mammalian oocytes and showed that organisms lacking RNA-dependent RNA polymerase (RdRP) activity can produce functional endogenous siRNAs from naturally occurring double-stranded RNAs. </p><p>Ghildiyal et al. (2008) independently identified 21-nucleotide endo-siRNAs that corresponded to transposons and heterochromatic sequences in the somatic cells of Drosophila melanogaster. Ghildiyal et al. (2008) also detected endo-siRNAs complementary to mRNAs; these siRNAs disproportionately mapped to the complementary regions of overlapping mRNAs predicted to form double-stranded RNA in vivo. Normal accumulation of somatic endo-siRNAs required the siRNA-generating ribonuclease Dicer2 and the RNA interference effector protein Ago2. Ghildiyal et al. (2008) proposed that endo-siRNAs generated by the fly RNAi pathway silence selfish genetic elements in the soma, much as Piwi-interacting RNAs do in the germline. </p><p>Kawamura et al. (2008) showed that in cultured Drosophila S2 cells, AGO2 associated with endogenous small RNAs of 20-22 nucleotides in length, which they had collectively named endogenous short interfering RNAs (esiRNAs). EsiRNAs can be divided into 2 groups: one that mainly corresponds to a subset of retrotransposons, and the other that arises from stem-loop structures. EsiRNAs are produced in a Dicer-2-dependent manner from distinctive genomic loci, are modified at the 3-prime ends, and can direct AGO2 to cleave target RNAs. Mutations in Dicer-2 caused an increase in retrotransposon transcripts. Kawamura et al. (2008) concluded that, together, their findings indicate that different types of small RNAs and Argonautes are used to repress retrotransposons in germline and somatic cells in Drosophila. </p><p>Czech et al. (2008) independently showed that Drosophila generated endogenous small interfering RNAs in both gonadal and somatic tissues. Production of these RNAs requires Dicer-2, but a subset depends preferentially on Loquacious (TARBP2; 605053) rather than the canonical Dicer-2 partner, R2D2. EsiRNAs arose both from the convergent transcription units and from structured genomic loci in a tissue-specific fashion. They predominantly join AGO2 and have the capacity, as a class, to target both protein-coding genes and mobile elements. Czech et al. (2008) concluded that these observations expand the repertoire of small RNAs in Drosophila, adding a class that blurs distinctions based on known biogenesis mechanisms and functional roles. </p><p>Okamura et al. (2008) reported that siRNAs derived from long hairpin RNA genes (hpRNA) program Slicer complexes that can repress endogenous target transcripts. The Drosophila hpRNA pathway is a hybrid mechanism that combines canonical RNA interference factors Dicer-2, Hen1 (C1ORF59; 612178), and AGO2 with a canonical microRNA factor Loquacious to generate approximately 21-nucleotide siRNAs. Okamura et al. (2008) concluded that these novel regulatory RNAs reveal unexpected complexity in the sorting of small RNAs, and open a window onto the biologic usage of endogenous RNA interference in Drosophila. </p><p>Merritt et al. (2008) observed decreased mRNA and protein expression of DICER1 and DROSHA (RNASEN; 608828) in 60 and 51%, respectively, of 111 invasive epithelial ovarian cancer (167000) specimens. Low DICER1 expression was significantly associated with advanced tumor stage (p = 0.007), and low DROSHA expression with suboptimal surgical cytoreduction (p = 0.02). Cancer specimens with both high DICER1 expression and high DROSHA expression were associated with increased median survival. Statistical analysis showed that low DICER1 expression was associated with decreased survival. Although rare missense variants were found in both genes, the presence or absence did not correlate with the level of expression. Functional assays indicated that gene silencing with shRNA, but not siRNA, may be impaired in cells with low DICER1 expression. The findings implicated a component of the RNA-interference machinery, which regulates gene expression, in the pathogenesis of ovarian cancer. Merritt et al. (2009) noted that 109 of the 111 samples used in the 2008 study had serous histologic features, of which 93 were high-grade and 16 low-grade tumors. </p><p>By multiple sequence alignment, Forman et al. (2008) identified highly conserved LET7-binding sequences within the coding regions of multiple genes, including DICER. Cotransfection experiments with human embryonic kidney 293 cells revealed that LET7 downregulated an expression vector containing only the DICER coding sequence, which contains 3 LET7-binding sites. Synonymous mutations of these LET7-binding sites permitted DICER expression. Experiments with a human colorectal cancer cell line suggested that processing of LET7 pre-miRNA by DICER was required for downregulation of DICER through its coding sequence in a negative-feedback loop. </p><p>Nakagawa et al. (2010) reported that inactivation of the C. elegans Dcr1 gene, which encodes the Dicer ribonuclease important for processing of small RNAs, compromises apoptosis and blocks apoptotic chromosome fragmentation. Dcr1 was cleaved by the Ced3 (601763) caspase to generate a C-terminal fragment with deoxyribonuclease activity, which produced 3-prime hydroxyl DNA breaks on chromosomes and promoted apoptosis. Thus, caspase-mediated activation of apoptotic DNA degradation is conserved. Nakagawa et al. (2010) concluded that Dcr1 functions in fragmenting chromosomal DNA during apoptosis in addition to processing small RNAs, and undergoes a protease-mediated conversion from a ribonuclease to a deoxyribonuclease. </p><p>Raaijmakers et al. (2010) demonstrated that deletion of Dicer1 specifically in mouse osteoprogenitors but not in mature osteoblasts disrupts the integrity of hematopoiesis. Myelodysplasia resulted and acute myelogenous leukemia emerged that had acquired several genetic abnormalities while having intact Dicer1. Examining gene expression altered in osteoprogenitors as a result of Dicer1 deletion showed reduced expression of Sbds (607444), the gene mutated in Shwachman-Bodian-Diamond syndrome (260400), a human bone marrow failure and leukemia predisposition condition. Deletion of Sbds in mouse osteoprogenitors induced bone marrow dysfunction with myelodysplasia. Therefore, Raaijmakers et al. (2010) concluded that perturbation of specific mesenchymal subsets of stromal cells can disorder differentiation, proliferation, and apoptosis of heterologous cells, and disrupt tissue homeostasis. Furthermore, Raaijmakers et al. (2010) concluded that primary stromal dysfunction can result in secondary neoplastic disease, supporting the concept of niche-induced oncogenesis. </p><p>In mice, Ago2 (EIF2C2; 606229) is uniquely required for viability, and only this Argonaute family member retains catalytic competence. To investigate the evolutionary pressure to conserve Argonaute enzymatic activity, Cheloufi et al. (2010) engineered a mouse with catalytically inactive Ago2 alleles. Homozygous mutants died shortly after birth with an obvious anemia. Examination of microRNAs and their potential targets revealed a loss of miR451 (612071), a small RNA important for erythropoiesis. Though this microRNA is processed by Drosha, its maturation does not require Dicer. Instead, the pre-miRNA becomes loaded into Ago and is cleaved by the Ago catalytic center to generate an intermediate 3-prime end, which is then further trimmed. Cheloufi et al. (2010) concluded that their findings linked the conservation of Argonaute catalysis to a conserved mechanism of microRNA biogenesis that is important for vertebrate development. </p><p>Su et al. (2010) showed that TAp63 (603273) suppresses tumorigenesis and metastasis, and coordinately regulates Dicer and miR130b (613682) to suppress metastasis. Metastatic mouse and human tumors deficient in TAp63 express Dicer at very low levels, and Su et al. (2010) found that modulation of expression of Dicer and miR130b markedly affected the metastatic potential of cells lacking TAp63. TAp63 binds to and transactivates the Dicer promoter, demonstrating direct transcriptional regulation of Dicer by TAp63. Su et al. (2010) concluded that their data provided a novel understanding of the roles of TAp63 in tumor and metastasis suppression through the coordinate transcriptional regulation of Dicer and miR130b, and may have implications for the many processes regulated by miRNAs. </p><p>Park et al. (2011) reported that human DICER anchors not only the 3-prime end of microRNAs but also the 5-prime end, with the cleavage site determined mainly by the distance (approximately 22 nucleotides) from the 5-prime end (5-prime counting rule). This cleavage requires a 5-prime-terminal phosphate group. Further, Park et al. (2011) identified a novel basic motif (5-prime pocket) in human DICER that recognizes the 5-prime phosphorylated end. The 5-prime counting rule and the 5-prime anchoring residues are conserved in Drosophila Dicer-1, but not in Giardia Dicer. Mutations in the 5-prime pocket reduce processing efficiency and alter cleavage sites in vitro. Consistently, miRNA biogenesis is perturbed in vivo when Dicer-null embryonic stem cells are replenished with the 5-prime-pocket mutant. Thus, Park et al. (2011) concluded that 5-prime end recognition by DICER is important for the precise and effective biogenesis of miRNAs. </p><p>Francia et al. (2012) demonstrated in human, mouse, and zebrafish that DICER and DROSHA (608828), but not downstream elements of the RNAi pathway, are necessary to activate the DNA damage response (DDR) upon exogenous DNA damage and oncogene-induced genotoxic stress, as studied by DDR foci formation and by checkpoint assays. DDR foci are sensitive to RNase A treatment, and DICER- and DROSHA-dependent RNA products are required to restore DDR foci in RNase-A-treated cells. Through RNA deep sequencing and the study of DDR activation at a single inducible DNA double-strand break, Francia et al. (2012) demonstrated that DDR foci formation requires site-specific DICER- and DROSHA-dependent small RNAs, named DDRNAs, which act in a MRE11-RAD50-NBS1-complex (see 602667)-dependent manner. DDRNAs, either chemically synthesized or in vitro generated by DICER cleavage, are sufficient to restore the DDR in RNase-A-treated cells, also in the absence of other cellular RNAs. </p><p>Kaneko et al. (2011) showed that DICER1 is reduced in the retinal pigment epithelium (RPE) of humans with geographic atrophy (see 603075) and that conditional ablation of DICER1, but not of 7 other microRNA processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induced accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA was increased in the RPE of humans with geographic atrophy, and this pathogenic RNA induced human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevented DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA could not induce RPE degeneration in mice. Kaneko et al. (2011) concluded that their findings revealed an miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, showed that Alu RNA can directly cause human pathology, and identified new targets for a major cause of blindness. </p><p>Using mouse and human RPE cells and mice lacking various genes, Tarallo et al. (2012) showed that a DICER1 deficit or Alu RNA exposure activated the NLRP3 (606416) inflammasome, triggering Toll-like receptor-independent MYD88 (602170) signaling via IL18 (600953) in the RPE. Inhibition of inflammasome components, MYD88, or IL18 prevented RPE degeneration induced by DICER1 loss or Alu RNA exposure. Because RPE in human geographic atrophy contained elevated NLRP3, PYCARD (606838), and IL18, Tarallo et al. (2012) suggested targeting this pathway for prevention and/or treatment of geographic atrophy. </p><p>Li et al. (2013) showed that infection of hamster cells and suckling mice by Nodamura virus, a mosquito-transmissible RNA virus, requires RNA interference suppression by its B2 protein. Loss of B2 expression or its suppressor activity leads to abundant production of viral siRNAs and rapid clearance of the mutant viruses in mice. However, viral small RNAs detected during virulent infection by Nodamura virus do not have the properties of canonical siRNAs. Maillard et al. (2013) demonstrated that undifferentiated mouse cells infected with encephalomyocarditis virus or Nodamura virus accumulate approximately 22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral double-strand RNA (dsRNA) replication intermediates, incorporate into Ago2 (606229), are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a Nodamura virus-encoded suppressor of RNAi that antagonizes Dicer during authentic infections reduces Nodamura virus accumulation, which is rescued in RNAi-deficient mouse cells. Maillard et al. (2013) concluded that antiviral RNA interference operates in mammalian cells. Li et al. (2013) concluded that their findings and those of Maillard et al. (2013) illustrated that Dicer-dependent processing of dsRNA viral replication intermediates into successive siRNAs is a conserved mammalian immune response to infection by 2 distinct positive-strand RNA viruses. </p><p>In mice, Dias et al. (2014) showed that beta-catenin (CTNNB1; 116806) mediates proresilient and anxiolytic effects in the nucleus accumbens, mediated by D2-type medium spiny neurons. Using genomewide beta-catenin enrichment mapping, Dias et al. (2014) identified Dicer1 as a beta-catenin target gene that mediates resilience. Small RNA profiling after excising beta-catenin from nucleus accumbens in the context of chronic stress revealed beta-catenin-dependent microRNA regulation associated with resilience. Dias et al. (2014) concluded that these findings established beta-catenin as a critical regulator in the development of behavioral resilience, activating a network that includes DICER1 and downstream microRNAs. The authors stated that this evidence presented a foundation for the development of novel therapeutic targets to promote stress resilience. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Copy Number Variation in Cancer</em></strong></p><p>
|
|
By examining DNA copy number in 283 known miRNA genes, Zhang et al. (2006) found a high proportion of copy number abnormalities in 227 human ovarian cancer, breast cancer, and melanoma specimens. Changes in miRNA copy number correlated with miRNA express. They also found a high frequency of copy number abnormalities of DICER1, AGO2 (606229), and other miRNA-associated genes in these cancers. Zhang et al. (2006) concluded that copy number alterations of miRNAs and their regulatory genes are highly prevalent in cancer and may account partly for the frequent miRNA gene deregulation reported in several tumor types. </p><p><strong><em>Pleuropulmonary Blastoma</em></strong></p><p>
|
|
Hill et al. (2009) demonstrated 10 loss-of-function and 1 missense mutation in the DICER1 gene (see, e.g., 606241.0001-606241.0005) leading to pleuropulmonary blastoma (PPB; 601200). In patients with tumors, there was loss of the wildtype allele within malignant areas in 6 of 7 the cases. </p><p>Bahubeshi et al. (2010) reported 2 unrelated families with cystic nephroma with or without PPB associated with different heterozygous mutations in the DICER1 gene in each family (see, e.g., 606241.0006). The findings added cystic nephroma to the phenotypic spectrum of PPB. Loss of heterozygosity at the DICER1 locus was not observed in tumor tissue. No germline DICER1 mutations were found in 50 children with Wilms tumor. </p><p><strong><em>Cervical Embryonal Rhabdomyosarcoma</em></strong></p><p>
|
|
Foulkes et al. (2011) stated that 40 different heterozygous germline mutations in DICER1 had been reported worldwide in 42 probands who developed pleuropulmonary blastoma (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors, or multinodular goiter as children or young adults. Foulkes et al. (2011) reported DICER1 mutations in 7 additional families manifesting uterine cervix embryonal rhabdomyosarcoma (CERMS, 4 cases), primitive neuroectodermal tumor (CPNET, 1 case), Wilms tumor (3 cases), pulmonary sequestration (1 case), and juvenile intestinal polyp (1 case). One mutation carrier in 1 family had complex cardiac defects, including transposition of the great arteries, bicuspid pulmonary valve, atrial septal defect, and small patent ductus arteriosus, and a mutation carrier in another family had pulmonary sequestration. Examination of tumor tissue from several patients did not show loss of heterozygosity for DICER1, indicating that some different second events must be required for tumor formation. However, the findings indicated that germline DICER1 mutations serve as a conditioning context for the development of multiple tumor types. </p><p><strong><em>Multinodular Goiter 1, with or without Sertoli-Leydig Cell Tumors</em></strong></p><p>
|
|
In affected members of 5 unrelated families with autosomal dominant multinodular goiter with or without Sertoli-Leydig cell tumors (MNG1; 138800), Rio Frio et al. (2011) identified 5 different heterozygous mutations in the DICER1 gene (see, e.g., 606241.0007-606241.0010). Four of the families had previously been reported by O'Brien and Wilansky (1981), Niedziela (2008), Bignell et al. (1997), and Druker et al. (1997). Studies of both types of tumors from several families showed no loss of heterozygosity at the DICER1 locus. Goiter tissue showed mixed immunostaining results, with some tissues showing no DICER1 protein staining and other tissues showing clear cytoplasmic staining. RNA studies from patient lymphoblasts showed perturbations of miRNA compared to controls, suggesting a dysregulation of gene expression patterns. In particular, LET7A (605386) and miR345 were both decreased in DICER1-related goiter tissue. </p><p><strong><em>Pineoblastoma</em></strong></p><p>
|
|
Sabbaghian et al. (2012) reported a single patient with a highly aggressive pineoblastoma due to germline frameshift mutation in DICER1. This tumor had loss of heterozygosity with loss of function of the wildtype allele of DICER1. Interestingly, it is possible for a tumor to survive without any DICER1 activity. </p><p><strong><em>Wilms Tumor</em></strong></p><p>
|
|
Rakheja et al. (2014) reported the whole-exome sequencing of 44 Wilms tumors (see WT1, 194070), identifying missense mutations in the microRNA (miRNA)-processing enzymes DROSHA (608828) and DICER1, and novel mutations in MYCN (164840), SMARCA4 (603254), and ARID1A (603024). Examination of tumor miRNA expression, in vitro processing assays, and genomic editing in human cells demonstrated that DICER1 and DROSHA mutations influence miRNA processing through distinct mechanisms. DICER1 RNase IIIB mutations preferentially impair processing of miRNAs deriving from the 5-prime arm of pre-miRNA hairpins, while DROSHA RNase IIIB mutations globally inhibit miRNA biogenesis through a dominant-negative mechanism. Both DROSHA and DICER1 mutations impair expression of tumor-suppressing miRNAs, including the LET7 family (see 605386), which are important regulators of MYCN, LIN28 (see 611043), and other Wilms tumor oncogenes. Rakheja et al. (2014) concluded that these results provided insights into the mechanisms through which mutations in miRNA biogenesis components reprogram miRNA expression in human cancer and suggested that these defects define a distinct subclass of Wilms tumors. </p><p>Palculict et al. (2016) identified 2 different heterozygous germline mutations in the DICER1 gene in affected members from 2 unrelated families with familial Wilms tumors. Eleven individuals in 1 family carried a heterozygous G803R mutation that was identified by whole-genome sequencing and confirmed by Sanger sequencing. Four individuals in this family had Wilms tumor, diagnosed between 38 and 57 months of age. Tumor tissue available from 1 patient showed homozygosity for the G803R mutation and loss of heterozygosity at the DICER1 locus. Some individuals in this family had phenotypes of so-called DICER1 syndrome, including cysts in the thyroid, lung, and kidney. The proband from the second family with Wilms tumor carried a heterozygous frameshift mutation (Arg800fsTer5) that was identified by direct sequencing of the DICER1 gene in 47 families. Tumor samples were not available from the second family. Penetrance appeared to be incomplete. </p><p><strong><em>GLOW Syndrome</em></strong></p><p>
|
|
In 2 unrelated patients with developmental delay, overgrowth, bilateral cystic lung lesions, and Wilms tumor (GLOW; 618272), Klein et al. (2014) detected 2 missense mutations in the DICER1 gene (606241.0013 and 606241.0014) present in the mosaic state. Tissue abundance of the mutated DICER DNA ranged from 21 to 37% in patient 1 and 28 to 47% in patient 2 in blood, tumor, and unaffected kidney samples. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>MicroRNAs have a central role in the development of plants, nematodes, and flies. These miRNAs are produced by the Dicer1 enzyme, which is conserved from fungi to vertebrates. To study its role in vertebrate development, Wienholds et al. (2003) cloned the zebrafish dicer1 ortholog and applied a method for target-selected gene inactivation. They observed an initial build-up of miRNA levels, produced by maternal Dicer1, in homozygous dicer1 mutants, but miRNA accumulation stopped after a few days. This resulted in developmental arrest around day 10. The results indicated that miRNA-producing Dicer1 is essential for vertebrate development. </p><p>Bernstein et al. (2003) disrupted the Dicer1 gene in mice. Loss of Dicer1 led to lethality early in development, with Dicer1-null embryos depleted of stem cells. Coupled with the inability to generate viable Dicer1-null embryonic stem (ES) cells, this suggested a role for Dicer and, by implication, the RNAi machinery in maintaining the stem cell population during early mouse development. </p><p>By conditional gene targeting, Kanellopoulou et al. (2005) disrupted the Dicer1 gene in mouse ES cells. Dicer-null ES cells were viable, despite being completely defective in RNA interference and generation of microRNAs. However, mutant ES cells displayed severe defects in differentiation both in vitro and in vivo. Epigenetic silencing of centromeric repeat sequences and expression of homologous small dsRNAs were markedly reduced. Reexpression of Dicer in knockout cells rescued these phenotypes. Kanellopoulou et al. (2005) concluded that Dicer participates in multiple, fundamental biologic processes, ranging from stem cell differentiation to maintenance of centromeric heterochromatin structure and centromeric silencing. </p><p>Yi et al. (2006) cloned more than 100 miRNAs from skin and showed that epidermis and hair follicles differentially express discrete miRNA families. To explore the functional significance of this finding, they conditionally targeted Dicer1 gene ablation in embryonic skin precursors. Within the first week after loss of miRNA expression, cell fate specification and differentiation were not markedly impaired, and in the interfollicular epidermis, apoptosis was not markedly increased. Notably, however, developing hair germs evaginated rather than invaginated, thereby perturbing the epidermal organization. Thus, Yi et al. (2006) characterized miRNAs in skin, the existence of which was hitherto unappreciated, and demonstrated their differential expression and importance in the morphogenesis of epithelial tissues within this vital organ. </p><p>Muljo et al. (2005) found that conditional deletion of the mouse Dcr1 gene in the T-cell lineage resulted in impaired T-cell development and aberrant T-helper (Th) cell differentiation and cytokine production. Deletion of Dcr1 in thymus led to a severe block in CD8 (see 186910)-positive T-cell development and reduced CD4 (186940)-positive T-cell numbers. The CD4-positive cells were defective in miRNA processing and, upon stimulation, proliferated poorly and underwent increased apoptosis. Dcr1-deficient Th cells preferentially expressed Ifng (147570), characteristic of helper cells of the Th1 lineage. Th2 cells lacking Dcr1 failed to silence Ifng expression. Muljo et al. (2005) proposed that the RNAi pathway may participate in epigenetic silencing of relevant genes during Th-cell lineage commitment. </p><p>Wang et al. (2006) demonstrated that an RNA interference pathway protects adult flies from infection by 2 evolutionarily diverse viruses. Their work also described a molecular framework for the viral immunity, in which viral double-stranded RNA produced during infection acts as the pathogen trigger whereas Drosophila Dicer-2 and Argonaute-2 (606228) act as host sensor and effector, respectively. Wang et al. (2006) concluded that their findings established a Drosophila model for studying the innate immunity against viruses in animals. </p><p>Drosophila have 2 Dicer genes: Dcr1, which controls production of miRNA, and Dcr2, which controls production of siRNA. Galiana-Arnoux et al. (2006) found that Drosophila with a loss-of-function function mutation in Dcr2 were more susceptible to 3 different families of RNA viruses. The viral protein B2, a potent inhibitor of processing of double-stranded RNA, was required for infection and killing of Drosophila. Galiana-Arnoux et al. (2006) concluded that RNA interference mechanisms are important in controlling virus replication in Drosophila. </p><p>Murchison et al. (2007) reported that targeted disruption of Dicer in mouse oocytes led to arrest in meiosis I with multiple disorganized spindles and severe chromosome congression defects. </p><p>To assess the role of miRNAs in cardiac development, Zhao et al. (2007) deleted Dicer in mouse heart. Mutant mice exhibited embryonic lethality by day 12.5, revealing an essential role for miRNA function in developing heart. </p><p>Using gene-trap methods, Otsuka et al. (2007) obtained mice functionally deficient in Dicer1 that did not undergo embryonic lethality due to hypomorphic Dicer1 expression. Analysis of viral growth in peritoneal macrophages of these mice revealed susceptibility to vesicular stomatitis virus (VSV) and herpes simplex-1 virus, but not to other viruses tested. Susceptibility to VSV was not due to increased VSV cell entry nor to deficiencies in type I interferon (e.g., IFNA; 147660) production or IFN responses. Reporter gene analysis of a mouse macrophage cell line transfected with plasmids containing VSV sequences showed that miR24 (see 609705) and miR93 (612984), which were expressed in the both the cell line and in peritoneal macrophages, targeted VSV genes encoding a viral RNA-dependent polymerase and a polymerase cofactor, respectively. Further analysis indicated that miR24 and miR93 suppressed VSV propagation in mouse macrophages. VSV lacking the miR24 and miR93 target sites was more pathogenic in wildtype mice than wildtype VSV. Otsuka et al. (2007) concluded that impairment of miR24 and miR93 production due to Dicer1 deficiency results in increased susceptibility to VSV. </p><p>Cuellar et al. (2008) created transgenic mice with targeted ablation of the Dicer1 gene in postmitotic dopaminoceptive neurons and found that the mice developed ataxia, front and hind limb clasping, and decreased life span with death occurring between 10 to 12 weeks of age. Postmortem examination showed reduced brain size, a reduction in miRNAs in the striatum, and smaller striatal neurons. The striatum showed astrogliosis but not neurodegeneration or neuronal loss. </p><p>Kobayashi et al. (2008) found that targeted deletion of Dicer1 in mouse cartilage resulted in progressive reduction in the proliferating pool of chondrocytes, leading to severe skeletal growth defects and premature death. Reduction of proliferating chondrocytes in Dicer1-null growth plates was caused by both decreased chondrocyte proliferation and accelerated differentiation into postmitotic hypertrophic chondrocytes. </p><p>Koralov et al. (2008) conditionally deleted Dicer in mouse early B-cell progenitors and observed a block in the pro- to pre-B cell transition. Gene expression profiling identified an miR17-92 (see 609416) signature in the 3-prime UTRs of genes upregulated in Dicer -/- pro-B cells, such as Bim (BCL2L11; 603827). Ablation of Bim or transgenic expression of Bcl2 (151430) partially rescued B-cell development. Dicer deficiency had no detectable effect on the developmental V(D)J recombination program, but it did affect antibody diversification by increasing the diversity of Ig-kappa variable regions through increased N sequence insertion and changing Dh element usage in the variable regions of IgH chains. </p><p>Chen et al. (2008) generated mice with cardiac-specific knockout of Dicer and observed rapidly progressive dilated cardiomyopathy (CMD; see 115200), heart failure, and postnatal lethality. Dicer-mutant mice showed misexpression of cardiac contractile proteins and profound sarcomere disarray. Functional analyses indicated significantly reduced heart rates and decreased fractional shortening of Dicer-mutant hearts. Dicer expression was also found to be decreased in failing human hearts in end-stage CMD, and a significant increase in Dicer expression was observed in those hearts after left ventricle assist devices were inserted to improve cardiac function. Chen et al. (2008) concluded that DICER and miRNAs have critical roles in normal cardiac function and under pathologic conditions. </p><p>Friedman et al. (2009) conditionally deleted Dicer in mouse inner ear sensory epithelium hair cells and in nonsensory supporting cells after their normal differentiation from progenitor cells. Removal of Dicer from sensory epithelium, which initially developed normally, caused abnormal growth and subsequent degeneration of mechanosensory hair cells, leading to deafness. </p><p>Using a conditional deletion approach, Dugas et al. (2010) generated mice lacking Dicer in oligodendrocytes and oligodendrocyte precursor cells. These mice developed a shivering phenotype that was associated with defects in myelination. Microarray analysis identified Mir219 (see MIR219-1; 611500), Mir138 (see MIR138-1; 613394), and Mir338 (614059) as the most highly induced miRNAs during oligodendrocyte differentiation. </p><p>Independently, Zhao et al. (2010) created mice lacking Dicer in oligodendrocyte lineage cells. Mutant mice were obtained at a mendelian ratio, but they developed severe tremor and ataxia due to myelinating defects and died around postnatal week 3. Microarray analysis revealed significantly reduced Mir219 and Mir338 expression in both Dicer-knockout and Olig1 (606385)-knockout oligodendrocytes. </p><p>Hebert et al. (2010) showed that absence of Dicer in the adult mouse forebrain was accompanied by a mixed neurodegenerative phenotype. Although neuronal loss was observed in the hippocampus, cellular shrinkage was predominant in the cortex. Neuronal degeneration coincided with the hyperphosphorylation of endogenous tau (157140) at several epitopes associated with neurofibrillary pathology. Transcriptome analysis of enzymes involved in tau phosphorylation identified ERK1 (MAPK3; 601795) as one of the candidate kinases responsible for this event in vivo. In addition, miRNAs belonging to the miR15 (609703) family were potent regulators of ERK1 expression in mouse neuronal cells and coexpressed with ERK1/2 in vivo. Finally, miR15a was specifically downregulated in Alzheimer disease (104300) brain. The authors hypothesized that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>14 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, LEU1583ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852976,
|
|
|
|
|
|
|
|
ClinVar: RCV000004725, RCV000240912
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with 3 individuals affected with pleuropulmonary blastoma (PPB; 601200) or lung cysts, Hill et al. (2009) identified a heterozygous T-to-G transversion at nucleotide 4930 in exon 23 of the DICER1 gene, resulting in a leu-to-arg substitution at codon 1583 (L1583R). The mutation affected an evolutionarily conserved amino acid. The nonpolar-to-polar change was not a previously reported sequence variant, nor was it detected in 360 cancer-free controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, GLU493TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852977,
|
|
|
|
|
|
|
|
ClinVar: RCV000004726, RCV000240918, RCV000493893, RCV004719621
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with 3 affected individuals, 1 with pleuropulmonary blastoma (PPB; 601200), 1 with lung cysts, and 1 with cystic nephroma, Hill et al. (2009) identified a heterozygous G-to-T transversion at nucleotide 1689 in exon 9 of DICER1, resulting in a glu-to-ter substitution at codon 493 (E493X). This mutation was associated with a reduced amount of mutant RNA and a loss of DICER1 staining in tumor-associated epithelium. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, ARG934TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852978,
|
|
|
|
|
|
|
|
ClinVar: RCV000004727, RCV000240862, RCV000493701, RCV004719622
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with pleuropulmonary blastoma (PPB; 601200), Hill et al. (2009) identified a heterozygous C-to-T transition at nucleotide 3012 in exon 18 of DICER1, resulting in an arg-to-ter substitution at codon 934 (R934X). Loss of DICER1 staining in tumor-associated epithelium was identified by immunohistochemistry. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, 1-BP INS, 2574A
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886037690,
|
|
|
|
|
|
|
|
ClinVar: RCV000240963, RCV000493145, RCV002282086
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with 2 affected individuals, 1 with pleuropulmonary blastoma (PPB; 601200) and the other with lung cysts, Hill et al. (2009) identified a heterozygous frameshift mutation resulting from insertion of an adenine at position 2574 in exon 15 of the DICER1 gene, resulting in a frameshift starting at codon 788 (T788Nfs). There was a reduced amount of mutant RNA from cell lines containing this mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, ARG534TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137852979,
|
|
|
|
|
|
|
|
ClinVar: RCV000004729, RCV000240896, RCV000851443, RCV004018561
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family with pleuropulmonary blastoma (PPB; 601200), Hill et al. (2009) identified a heterozygous C-to-T transition at nucleotide 1812 in exon 10 of the DICER1 gene, resulting in an arg-to-ter substitution at codon 534 (R534X). This mutation was associated with loss of DICER1 staining in tumor-associated epithelium. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 PLEUROPULMONARY BLASTOMA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
GOITER, MULTINODULAR 1, WITH OR WITHOUT SERTOLI-LEYDIG CELL TUMORS, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, SER1826TER
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1595314576,
|
|
|
|
|
|
|
|
ClinVar: RCV000023521, RCV000023522, RCV001201154
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with pleuropulmonary blastoma (PPB; 601200) and cystic nephroma, Bahubeshi et al. (2010) identified a heterozygous 5477C-A transversion in exon 25 of the DICER1 gene, resulting in a ser1826-to-ter (S1826X) substitution that would exclude the double-stranded RNA-binding domain. The patient died at age 5 years. Her brother, who also carried the mutation, had cystic nephroma without PPB and was alive at age 5 years. Heterozygosity for the mutation was also found in the mother, who had goiter (MNG1; 138800) and in 2 unaffected sisters of the proband. There were 2 other maternal relatives with goiter, but DNA was not studied. In cystic nephroma tissue derived from the brother, there was no loss of heterozygosity at the DICER1 locus, but there was decreased immunostaining for the protein in renal tubules. The findings indicated that nephroma can be a part of the PPB spectrum and also illustrated that DICER1 mutations can predispose to goiter. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 GOITER, MULTINODULAR 1, WITH OR WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, 4-BP DEL, 871AAAG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1595447577,
|
|
|
|
|
|
|
|
ClinVar: RCV000023523
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 members of a family with multinodular goiter with or without Sertoli-Leydig cell tumors (MNG1; 138800), Rio Frio et al. (2011) identified a heterozygous 4-bp deletion (871delAAAG) in the DICER1 gene, resulting in a frameshift and premature termination. A mutant mRNA could not be detected due to nonsense-mediated mRNA decay. The family had originally been reported by O'Brien and Wilansky (1981). The female proband had multinodular goiter at age 16 years and an ovarian Sertoli-Leydig cell tumor at age 18; 3 additional family members with the mutation had multinodular goiter only. Studies of the ovarian tumor showed no loss of heterozygosity for the DICER1 locus. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 GOITER, MULTINODULAR 1, WITH OR WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, 2457C-G
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1595380836,
|
|
|
|
|
|
|
|
ClinVar: RCV000023525, RCV001201008
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a family with multinodular goiter with or without Sertoli-Leydig cell tumors (MNG1; 138800), Rio Frio et al. (2011) identified a heterozygous 2457C-G transversion in exon 16 of the DICER1 gene, resulting in a de novo splice site and an in-frame deletion of the first 21 bps of exon 16 (2437_2457del21). The mutant transcript generates a predicted DICER1 protein lacking amino acids ile813 to tyr819, resulting in an altered PAZ structure. The family had previously been reported by Niedziela (2008). The proband developed multinodular goiter at age 9 years and an ovarian Sertoli-Leydig cell tumor at age 14. Two other family members developed multinodular goiter only at ages 12 and 17, respectively. There was no loss of heterozygosity at the DICER1 locus in tumor tissue, and immunohistochemical studies showed loss of protein staining in the goiter, intense staining in Sertoli cells, and weak staining in Leydig cells. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 GOITER, MULTINODULAR 1, WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER, SER839PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs387906934,
|
|
|
|
|
|
|
|
ClinVar: RCV000023526, RCV001201061, RCV002426517
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Canadian family with multinodular goiter without Sertoli-Leydig cell tumors (MNG1; 138800) reported by Bignell et al. (1997), Rio Frio et al. (2011) identified a heterozygous 2916C-T transition in the DICER1 gene, resulting in a ser839-to-phe (S839F) substitution in a highly conserved residue and predicted to disrupt an alpha-helix in the PAZ domain. The mutation was not found in 455 controls. The mutation was found in all 20 affected individuals and in none of 10 unaffected family members. There was no loss of heterozygosity at the DICER1 locus in tumor tissues analyzed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 GOITER, MULTINODULAR 1, WITHOUT SERTOLI-LEYDIG CELL TUMORS</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, IVS17AS, G-T, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1595374375,
|
|
|
|
|
|
|
|
ClinVar: RCV000023524, RCV001201069
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Canadian family with multinodular goiter (MNG1; 138800) originally reported by Druker et al. (1997), Rio Frio et al. (2011) identified a heterozygous G-to-T transversion in intron 17 of the DICER1 gene, affecting a splice site and resulting in an in-frame deletion of exon 18, eliminating part of the PAZ domain. The mutation was not seen in 430 controls. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 RHABDOMYOSARCOMA, EMBRYONAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, 2-BP DEL, 3097CT
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886037650,
|
|
|
|
|
|
|
|
ClinVar: RCV000056332, RCV001201022
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which the proband had a cervical embryonal rhabdomyosarcoma (CERMS; see 180295) and multinodular goiter (see 138800), Foulkes et al. (2011) identified a heterozygous mutation in exon 21 of the DICER1 gene, a 2-basepair deletion (c.3907_3908delCT) that resulted in frameshift and premature termination (Leu1303ValfsTer4). Other mutation carriers in the family had multinodular goiter, lung cysts, esophageal hamartomatous polyp, and/or thyroid nodule. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 RHABDOMYOSARCOMA, EMBRYONAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, 6-BP DEL/1-BP INS, NT3611
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs886037651,
|
|
|
|
|
|
|
|
ClinVar: RCV000056333, RCV001201011
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a family in which 2 members had cervical embryonal rhabdomyosarcoma (CERMS; see 180295), Foulkes et al. (2011) identified a heterozygous indel mutation in exon 21 of the DICER1 gene (c.3611_3616delACTACAinsT) that resulted in frameshift and premature termination (Tyr1204LeufsTer29). The proband had lung cysts and multinodular goiter in addition to CERMS; other mutation carriers in the family had Sertoli-Leydig cell tumor, multinodular goiter, and pleomorphic sarcoma. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 GLOW SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, ASP1713VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1595331224,
|
|
|
|
|
|
|
|
ClinVar: RCV000735852, RCV000851425, RCV001201032
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with global developmental delay, lung cysts, overgrowth, and Wilms tumor (GLOW; 618272), Klein et al. (2014) identified a heterozygous A-to-T transversion at nucleotide 5138 of the DICER1 gene resulting in a valine substitution for the aspartic acid at codon 1713 (D1713V). Aspartic acid-1713 is highly conserved through evolution, and the mutation in this patient is 13 bp from the mutation in the second patient identified by the authors (606241.0014), which occurred at a known metal binding site essential for DICER1 RNase IIIb domain function. The mutation was identified by whole-exome sequencing of DNA from peripheral mononuclear blood cells. The mutation occurred as a postzygotic event as it was absent from both parents and present in varying abundance in different tissues. Klein et al. (2014) stated that the variant was absent from the EVS database and UCLA clinical genomics dataset. Hamosh (2018) noted that the variant was not present in the gnomAD database (December 30, 2018). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 GLOW SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
DICER1, ASP1709TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1595331264,
|
|
|
|
|
|
|
|
ClinVar: RCV000735853, RCV001200978
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with global developmental delay, lung cysts, overgrowth, and Wilms tumor (GLOW; 618272), Klein et al. (2014) identified a heterozygous G-to-T transversion at nucleotide 5125 of the DICER1 gene, resulting in an aspartic acid-to-tyrosine substitution at codon 1709 (D1709Y). The aspartic acid at position 1709 is highly conserved and functions as part of a metal binding site essential for 5-prime microRNA cleavage from mature pre-microRNAs and a hotspot for somatic mutations in cancers. Hamosh (2018) noted that the variant was not present in the gnomAD database (December 30, 2018). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bahubeshi, A., Bal, N., Rio Frio, T., Hamel, N., Pouchet, C., Yilmaz, A., Bouron-Dal Soglio, D., Williams, G. M., Tischkowitz, M., Priest, J. R., Foulkes, W. D.
|
|
<strong>Germline DICER1 mutations and familial cystic nephroma.</strong>
|
|
J. Med. Genet. 47: 863-866, 2010.
|
|
|
|
|
|
[PubMed: 21036787]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2010.081216]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bernstein, E., Kim, S. Y., Carmell, M. A., Murchison, E. P., Alcorn, H., Li, M. Z., Mills, A. A., Elledge, S. J., Anderson, K. V., Hannon, G. J.
|
|
<strong>Dicer is essential for mouse development.</strong>
|
|
Nature Genet. 35: 215-216, 2003. Note: Erratum: Nature Genet. 35: 287 only, 2003.
|
|
|
|
|
|
[PubMed: 14528307]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1253]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bignell, G. R., Canzian, F., Shayeghi, M., Stark, M., Shugart, Y. Y., Biggs, P., Mangion, J., Hamoudi, R., Rosenblatt, J., Buu, P., Sun, S., Stoffer, S. S., Goldgar, D. E., Romeo, G., Houlston, R. S., Narod, S. A., Stratton, M. R., Foulkes, W. D.
|
|
<strong>Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.</strong>
|
|
Am. J. Hum. Genet. 61: 1123-1130, 1997.
|
|
|
|
|
|
[PubMed: 9345104]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/301610]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Blaszczyk, J., Tropea, J. E., Bubunenenko, M., Routzahn, K. M., Waugh, D. S., Court, D. L., Ji, X.
|
|
<strong>Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage.</strong>
|
|
Structure 9: 1225-1236, 2001.
|
|
|
|
|
|
[PubMed: 11738048]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0969-2126(01)00685-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cheloufi, S., Dos Santos, C. O., Chong, M. M. W., Hannon, G. J.
|
|
<strong>A Dicer-independent miRNA biogenesis pathway that requires Ago catalysis.</strong>
|
|
Nature 465: 584-589, 2010.
|
|
|
|
|
|
[PubMed: 20424607]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09092]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chen, J.-F., Murchison, E. P., Tang, R., Callis, T. E., Tatsuguchi, M., Deng, Z., Rojas, M., Hammond, S. M., Schneider, M. D., Selzman, C. H., Meissner, G., Patterson, C., Hannon, G. J., Wang, D.-Z.
|
|
<strong>Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 2111-2116, 2008.
|
|
|
|
|
|
[PubMed: 18256189]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0710228105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chendrimada, T. P., Gregory, R. I., Kumaraswamy, E., Norman, J., Cooch, N., Nishikura, K., Shiekhattar, R.
|
|
<strong>TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. (Letter)</strong>
|
|
Nature 436: 740-744, 2005.
|
|
|
|
|
|
[PubMed: 15973356]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature03868]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cuellar, T. L., Davis, T. H., Nelson, P. T., Loeb, G. B., Harfe, B. D., Ullian, E., McManus, M. T.
|
|
<strong>Dicer loss in striatal neurons produces behavioral and neuroanatomical phenotypes in the absence of neurodegeneration.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 5614-5619, 2008.
|
|
|
|
|
|
[PubMed: 18385371]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0801689105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Czech, B., Malone, C. D., Zhou, R., Stark, A., Schlingeheyde, C., Dus, M., Perrimon, N., Kellis, M., Wohlschlegel, J. A., Sachidanandam, R., Hannon, G. J., Brennecke, J.
|
|
<strong>An endogenous small interfering RNA pathway in Drosophila.</strong>
|
|
Nature 453: 798-802, 2008.
|
|
|
|
|
|
[PubMed: 18463631]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature07007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dias, C., Feng, J., Sun, H., Shao, N., Mazei-Robison, M. S., Damez-Werno, D., Scobie, K., Bagot, R., LaBonte, B., Ribeiro, E., Liu, X., Kennedy, P., and 11 others.
|
|
<strong>Beta-catenin mediates stress resilience through Dicer1/microRNA regulation.</strong>
|
|
Nature 516: 51-55, 2014.
|
|
|
|
|
|
[PubMed: 25383518]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature13976]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Druker, H. A., Kasprzak, L., Begin, L. R., Jothy, S., Narod, S. A., Foulkes, W. D.
|
|
<strong>Family with Graves disease, multinodular goiter, nonmedullary thyroid carcinoma, and alveolar rhabdomyosarcoma.</strong>
|
|
Am. J. Med. Genet. 72: 30-33, 1997.
|
|
|
|
|
|
[PubMed: 9295070]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dugas, J. C., Cuellar, T. L., Scholze, A., Ason, B., Ibrahim, A., Emery, B., Zamanian, J. L., Foo, L. C., McManus, M. T., Barres, B. A.
|
|
<strong>Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination.</strong>
|
|
Neuron 65: 597-611, 2010.
|
|
|
|
|
|
[PubMed: 20223197]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2010.01.027]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Forman, J. J., Legesse-Miller, A., Coller, H. A.
|
|
<strong>A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 14879-14884, 2008.
|
|
|
|
|
|
[PubMed: 18812516]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0803230105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Foulkes, W. D., Bahubeshi, A., Hamel, N., Pasini, B., Asioli, S., Baynam, G., Choong, C. S., Charles, A., Frieder, R. P., Dishop, M. K., Graf, N., Ekim, M., Bouron-Dal Soglio, D., Arseneau, J., Young, R. H., Sabbaghian, N., Srivastava, A., Tischkowitz, M. D., Priest, J. R.
|
|
<strong>Extending the phenotypes associated with DICER1 mutations.</strong>
|
|
Hum. Mutat. 32: 1381-1384, 2011.
|
|
|
|
|
|
[PubMed: 21882293]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.21600]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Francia, S., Michelini, F., Saxena, A., Tang, D., de Hoon, M., Anelli, V., Mione, M., Carninci, P., d'Adda di Fagagna, F.
|
|
<strong>Site-specific DICER and DROSHA RNA products control the DNA-damage response.</strong>
|
|
Nature 488: 231-235, 2012.
|
|
|
|
|
|
[PubMed: 22722852]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11179]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Friedman, L. M., Dror, A. A., Mor, E., Tenne, T., Toren, G., Satoh, T., Biesemeier, D. J., Shomron, N., Fekete, D. M., Hornstein, E., Avraham, K. B.
|
|
<strong>MicroRNAs are essential for development and function of inner ear hair cells in vertebrates.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 7915-7920, 2009.
|
|
|
|
|
|
[PubMed: 19416898]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0812446106]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Galiana-Arnoux, D., Dostert, C., Schneemann, A., Hoffmann, J. A., Imler, J.-L.
|
|
<strong>Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila.</strong>
|
|
Nature Immun. 7: 590-597, 2006.
|
|
|
|
|
|
[PubMed: 16554838]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ni1335]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ghildiyal, M., Seitz, H., Horwich, M. D., Li, C., Du, T., Lee, S., Xu, J., Kittler, E. L. W., Zapp, M. L., Weng, Z., Zamore, P. D.
|
|
<strong>Endogenous siRNAs derived from transposons and mRNAs in Drosophila somatic cells.</strong>
|
|
Science 320: 1077-1081, 2008.
|
|
|
|
|
|
[PubMed: 18403677]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1157396]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Giraldez, A. J., Mishima, Y., Rihel, J., Grocock, R. J., Van Dongen, S., Inoue, K., Enright, A. J., Schier, A. F.
|
|
<strong>Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs.</strong>
|
|
Science 312: 75-79, 2006.
|
|
|
|
|
|
[PubMed: 16484454]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1122689]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gregory, R. I., Chendrimada, T. P., Cooch, N., Shiekhattar, R.
|
|
<strong>Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.</strong>
|
|
Cell 123: 631-640, 2005.
|
|
|
|
|
|
[PubMed: 16271387]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2005.10.022]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamosh, A.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 12/30/2018.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hatfield, S. D., Shcherbata, H. R., Fischer, K. A., Nakahara, K., Carthew, R. W., Ruohola-Baker, H.
|
|
<strong>Stem cell division is regulated by the microRNA pathway. (Letter)</strong>
|
|
Nature 435: 974-978, 2005.
|
|
|
|
|
|
[PubMed: 15944714]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature03816]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hebert, A. S., Papadopoulou, A. S., Smith, P., Galas, M.-C., Planel, E., Silahtaroglu, A. N., Sergeant, N., Buee, L., De Strooper, B.
|
|
<strong>Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration.</strong>
|
|
Hum. Molec. Genet. 19: 3959-3969, 2010.
|
|
|
|
|
|
[PubMed: 20660113]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddq311]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hill, D. A., Ivanovich, J., Priest, J. R., Gurnett, C. A., Dehner, L. P., Desruisseau, D., Jarzembowski, J. A., Wilkenheiser-Brokamp, K. A., Suarez, B. K., Whelan, A. J., Williams, G., Bracamontes, D., Messinger, Y., Goodfellow, P. J.
|
|
<strong>DICER1 mutations in familial pleuropulmonary blastoma.</strong>
|
|
Science 325: 965 only, 2009.
|
|
|
|
|
|
[PubMed: 19556464]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1174334]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hutvagner, G., McLachlan, J., Pasquinelli, A. E., Balint, E., Tuschl, T., Zamore, P. D.
|
|
<strong>A cellular function for the RNA-interference enzyme dicer in the maturation of the let-7 small temporal RNA.</strong>
|
|
Science 293: 834-838, 2001.
|
|
|
|
|
|
[PubMed: 11452083]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1062961]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jing, Q., Huang, S., Guth, S., Zarubin, T., Motoyama, A., Chen, J., Di Padova, F., Lin, S.-C., Gram, H., Han, J.
|
|
<strong>Involvement of microRNA in AU-rich element-mediated mRNA instability.</strong>
|
|
Cell 120: 623-634, 2005.
|
|
|
|
|
|
[PubMed: 15766526]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2004.12.038]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kaneko, H., Dridi, S., Tarallo, V., Gelfand, B. D., Fowler, B. J., Cho, W. G., Kleinman, M. E., Ponicsan, S. L., Hauswirth, W. W., Chiodo, V. A., Kariko, K., Yoo, J. W., and 30 others.
|
|
<strong>DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration.</strong>
|
|
Nature 471: 325-330, 2011.
|
|
|
|
|
|
[PubMed: 21297615]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09830]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kanellopoulou, C., Muljo, S. A., Kung, A. L., Ganesan, S., Drapkin, R., Jenuwein, T., Livingston, D. M., Rajewsky, K.
|
|
<strong>Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing.</strong>
|
|
Genes Dev. 19: 489-501, 2005.
|
|
|
|
|
|
[PubMed: 15713842]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.1248505]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kawamura, Y., Saito, K., Kin, T., Ono, Y., Asai, K., Sunohara, T., Okada, T. N., Siomi, M. C., Siomi, H.
|
|
<strong>Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells.</strong>
|
|
Nature 453: 793-797, 2008.
|
|
|
|
|
|
[PubMed: 18463636]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature06938]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Klein, S., Lee, H., Ghahremani, S., Kempert, P., Ischander, M., Teitell, M. A., Nelson, S. F., Martinez-Agosto, J. A.
|
|
<strong>Expanding the phenotype of mutations in DICER1: mosaic missense mutations in the RNase IIIb domain of DICER1 cause GLOW syndrome.</strong>
|
|
J. Med. Genet. 51: 294-302, 2014.
|
|
|
|
|
|
[PubMed: 24676357]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2013-101943]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kobayashi, T., Lu, J., Cobb, B. S., Rodda, S. J., McMahon, A. P., Schipani, E., Merkenschlager, M., Kronenberg, H. M.
|
|
<strong>Dicer-dependent pathways regulate chondrocyte proliferation and differentiation.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 1949-1954, 2008.
|
|
|
|
|
|
[PubMed: 18238902]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0707900105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Koralov, S. B., Muljo, S. A., Galler, G. R., Krek, A., Chakraborty, T., Kanellopoulou, C., Jensen, K., Cobb, B. S., Merkenschlager, M., Rajewsky, N., Rajewsky, K.
|
|
<strong>Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage.</strong>
|
|
Cell 132: 860-874, 2008.
|
|
|
|
|
|
[PubMed: 18329371]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2008.02.020]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, Y., Lu, J., Han, Y., Fan, X., Ding, S.-W.
|
|
<strong>RNA interference functions as an antiviral immunity mechanism in mammals.</strong>
|
|
Science 342: 231-234, 2013.
|
|
|
|
|
|
[PubMed: 24115437]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1241911]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
MacRae, I. J., Zhou, K., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., Adams, P. D., Doudna, J. A.
|
|
<strong>Structural basis for double-stranded RNA processing by Dicer.</strong>
|
|
Science 311: 195-198, 2006.
|
|
|
|
|
|
[PubMed: 16410517]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1121638]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maillard, P. V., Ciaudo, C., Marchais, A., Li, Y., Jay, F., Ding, S. W., Voinnet, O.
|
|
<strong>Antiviral RNA interference in mammalian cells.</strong>
|
|
Science 342: 235-238, 2013.
|
|
|
|
|
|
[PubMed: 24115438]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1241930]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Maniataki, E., Mourelatos, Z.
|
|
<strong>A human, ATP-independent, RISC assembly machine fueled by pre-miRNA.</strong>
|
|
Genes Dev. 19: 2979-2990, 2005.
|
|
|
|
|
|
[PubMed: 16357216]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.1384005]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuda, S., Ichigotani, Y., Okuda, T., Irimura, T., Nakatsugawa, S., Hamaguchi, M.
|
|
<strong>Molecular cloning and characterization of a novel human gene (HERNA) which encodes a putative RNA-helicase.</strong>
|
|
Biochim. Biophys. Acta 1490: 163-169, 2000.
|
|
|
|
|
|
[PubMed: 10786632]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0167-4781(99)00221-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Merritt, W. M., Lin, Y. G., Han, L. Y., Kamat, A. A., Spannuth, W. A., Schmandt, R., Urbauer, D., Pennacchio, L. A., Cheng, J.-F., Nick, A. M., Deavers, M. T., Mourad-Zeidan, A., and 10 others.
|
|
<strong>Dicer, Drosha, and outcomes in patients with ovarian cancer.</strong>
|
|
New Eng. J. Med. 359: 2641-2650, 2008. Note: Erratum: New Eng. J. Med. 363: 1877 only, 2010.
|
|
|
|
|
|
[PubMed: 19092150]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa0803785]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Merritt, W. M., Urbauer, D. L., Sood, A. K.
|
|
<strong>Reply to Kobel et al. (Letter)</strong>
|
|
New Eng. J. Med. 360: 1151 only, 2009.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Muljo, S. A., Ansel, K. M., Kanellopoulou, C., Livingston, D. M., Rao, A., Rajewsky, K.
|
|
<strong>Aberrant T cell differentiation in the absence of Dicer.</strong>
|
|
J. Exp. Med. 202: 261-269, 2005.
|
|
|
|
|
|
[PubMed: 16009718]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1084/jem.20050678]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murchison, E. P., Stein, P., Xuan, Z., Pan, H., Zhang, M. Q., Schultz, R. M., Hannon, G. J.
|
|
<strong>Critical roles for Dicer in the female germline.</strong>
|
|
Genes Dev. 21: 682-693, 2007.
|
|
|
|
|
|
[PubMed: 17369401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.1521307]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nakagawa, A., Shi, Y., Kage-Nakadai, E., Mitani, S., Xue, D.
|
|
<strong>Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease.</strong>
|
|
Science 328: 327-334, 2010.
|
|
|
|
|
|
[PubMed: 20223951]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1182374]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Niedziela, M.
|
|
<strong>Virilizing ovarian tumor in a 14-year-old female with a prior familial multinodular goiter.</strong>
|
|
Pediat. Blood Cancer 51: 543-545, 2008.
|
|
|
|
|
|
[PubMed: 18570301]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/pbc.21675]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
O'Brien, P. K., Wilansky, D. L.
|
|
<strong>Familial thyroid nodulation and arrhenoblastoma.</strong>
|
|
Am. J. Clin. Path. 75: 578-581, 1981.
|
|
|
|
|
|
[PubMed: 6261577]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/ajcp/75.4.578]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Okamura, K., Chung, W.-J., Ruby, J. G., Guo, H., Bartel, D. P., Lai, E. C.
|
|
<strong>The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs.</strong>
|
|
Nature 453: 803-806, 2008.
|
|
|
|
|
|
[PubMed: 18463630]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature07015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Otsuka, M., Jing, Q., Georgel, P., New, L., Chen, J., Mols, J., Kang, Y. J., Jiang, Z., Du, X., Cook, R., Das, S. C., Pattnaik, A. K., Beutler, B., Han, J.
|
|
<strong>Hypersusceptibility to vesicular stomatitis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression.</strong>
|
|
Immunity 27: 123-134, 2007.
|
|
|
|
|
|
[PubMed: 17613256]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.immuni.2007.05.014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Palculict, T. B., Ruteshouser, E. C., Fan, Y., Wang, W., Strong, L., Huff, V.
|
|
<strong>Identification of germline DICER1 mutations and loss of heterozygosity in familial Wilms tumour.</strong>
|
|
J. Med. Genet. 53: 385-388, 2016.
|
|
|
|
|
|
[PubMed: 26566882]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2015-103311]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Park, J.-E., Heo, I., Tian, Y., Simanshu, D. K., Chang, H., Jee, D., Patel, D. J., Kim, V. N.
|
|
<strong>Dicer recognizes the 5-prime end of RNA for efficient and accurate processing.</strong>
|
|
Nature 475: 201-205, 2011.
|
|
|
|
|
|
[PubMed: 21753850]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10198]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Provost, P., Samuelsson, B., Radmark, O.
|
|
<strong>Interaction of 5-lipoxygenase with cellular proteins.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 1881-1885, 1999.
|
|
|
|
|
|
[PubMed: 10051563]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.5.1881]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raaijmakers, M. H. G. P., Mukherjee, S., Guo, S., Zhang, S., Kobayashi, T., Schoonmaker, J. A., Ebert, B. L., Al-Shahrour, F., Hasserjian, R. P., Scadden, E. O., Aung, Z., Matza, M., Merkenschlager, M., Lin, C., Rommens, J. M., Scadden, D. T.
|
|
<strong>Bone progenitor dysfunction induces myelodysplasia and secondary leukaemia.</strong>
|
|
Nature 464: 852-857, 2010.
|
|
|
|
|
|
[PubMed: 20305640]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature08851]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rakheja, D., Chen, K. S., Liu, Y., Shukla, A. A., Schmid, V., Chang, T.-C., Khokhar, S., Wickiser, J. E., Karandikar, N. J., Malter, J. S., Mendell, J. T., Amatruda, J. F.
|
|
<strong>Somatic mutations in DROSHA and DICER1 impair microRNA biogenesis through distinct mechanisms in Wilms tumours.</strong>
|
|
Nature Commun. 5: 4802, 2014. Note: Electronic Article. Erratum: Nature Commun. 8: 16177, 2017.
|
|
|
|
|
|
[PubMed: 25190313]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ncomms5802]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rio Frio, T., Bahubeshi, A., Kanellopoulou, C., Hamel, N., Niedziela, M., Sabbaghian, N., Pouchet, C., Gilbert, L., O'Brien, P. K., Serfas, K., Broderick, P., Houlston, R. S., and 13 others.
|
|
<strong>DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli-Leydig cell tumors.</strong>
|
|
J.A.M.A. 305: 68-77, 2011.
|
|
|
|
|
|
[PubMed: 21205968]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/jama.2010.1910]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sabbaghian, N., Hamel, N., Srivastava, A., Albrecht, S., Priest, J. R., Foulkes, W. D.
|
|
<strong>Germline DICER1 mutation and associated loss of heterozygosity in a pineoblastoma.</strong>
|
|
J. Med. Genet. 49: 417-419, 2012.
|
|
|
|
|
|
[PubMed: 22717647]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2012-100898]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Su, X., Chakravarti, D., Cho, M. S., Liu, L., Gi, Y. J., Lin, Y.-L., Leung, M. L., El-Naggar, A., Creighton, C. J., Suraokar, M. B., Wistuba, I., Flores, E. R.
|
|
<strong>TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs.</strong>
|
|
Nature 467: 986-990, 2010. Note: Erratum: Nature 632: E2, 2024.
|
|
|
|
|
|
[PubMed: 20962848]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09459]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tam, O. H., Aravin, A. A., Stein, P., Girard, A., Murchison, E. P., Cheloufi, S., Hodges, E., Anger, M., Sachidanandam, R., Schultz, R. M., Hannon, G. J.
|
|
<strong>Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes.</strong>
|
|
Nature 453: 534-538, 2008.
|
|
|
|
|
|
[PubMed: 18404147]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature06904]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., Albuquerque, R. J. C., Hauswirth, W. W., and 17 others.
|
|
<strong>DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88.</strong>
|
|
Cell 149: 847-859, 2012.
|
|
|
|
|
|
[PubMed: 22541070]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2012.03.036]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tomari, Y., Matranga, C., Haley, B., Martinez, N., Zamore, P. D.
|
|
<strong>A protein sensor for siRNA asymmetry.</strong>
|
|
Science 306: 1377-1380, 2004.
|
|
|
|
|
|
[PubMed: 15550672]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1102755]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Volpe, T. A., Kidner, C., Hall, I. M., Teng, G., Grewal, S. I. S., Martienssen, R. A.
|
|
<strong>Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi.</strong>
|
|
Science 297: 1833-1837, 2002.
|
|
|
|
|
|
[PubMed: 12193640]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1074973]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, X.-H., Aliyari, R., Li, W.-X., Li, H.-W., Kim, K., Carthew, R., Atkinson, P., Ding, S.-W.
|
|
<strong>RNA interference directs innate immunity against viruses in adult Drosophila.</strong>
|
|
Science 312: 452-454, 2006.
|
|
|
|
|
|
[PubMed: 16556799]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1125694]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Watanabe, T., Totoki, Y., Toyoda, A., Kaneda, M., Kuramochi-Miyagawa, S., Obata, Y., Chiba, H., Kohara, Y., Kono, T., Nakano, T., Surani, M. A., Sakaki, Y., Sasaki, H.
|
|
<strong>Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes.</strong>
|
|
Nature 453: 539-543, 2008.
|
|
|
|
|
|
[PubMed: 18404146]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature06908]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wienholds, E., Koudijs, M. J., van Eeden, F. J. M., Cuppen, E., Plasterk, R. H. A.
|
|
<strong>The microRNA-producing enzyme Dicer1 is essential for zebrafish development.</strong>
|
|
Nature Genet. 35: 217-218, 2003.
|
|
|
|
|
|
[PubMed: 14528306]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1251]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yi, R., O'Carroll, D., Pasolli, H. A., Zhang, Z., Dietrich, F. S., Tarakhovsky, A., Fuchs, E.
|
|
<strong>Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs.</strong>
|
|
Nature Genet. 38: 356-362, 2006.
|
|
|
|
|
|
[PubMed: 16462742]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1744]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E., Filipowicz, W.
|
|
<strong>Single processing center models for human Dicer and bacterial RNase III.</strong>
|
|
Cell 118: 57-68, 2004.
|
|
|
|
|
|
[PubMed: 15242644]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2004.06.017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhang, L., Huang, J., Yang, N., Greshock, J., Megraw, M. S., Giannakakis, A., Liang, S., Naylor, T. L., Barchetti, A., Ward, M. R., Yao, G., Medina, A., O'Brien-Jenkins, A., Katsaros, D., Hatzigeorgiou, A., Gimotty, P. A., Weber, B. L., Coukos, G.
|
|
<strong>MicroRNAs exhibit high frequency genomic alterations in human cancer.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 9136-9141, 2006.
|
|
|
|
|
|
[PubMed: 16754881]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0508889103]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhao, X., He, X., Han, X., Yu, Y., Ye, F., Chen, Y., Hoang, T., Xu, X., Mi, Q.-S., Xin, M., Wang, F., Appel, B., Lu, Q. R.
|
|
<strong>MicroRNA-mediated control of oligodendrocyte differentiation.</strong>
|
|
Neuron 65: 612-626, 2010.
|
|
|
|
|
|
[PubMed: 20223198]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.neuron.2010.02.018]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhao, Y., Ransom, J. F., Li, A., Vedantham, V., von Drehle, M., Muth, A. N., Tsuchihashi, T., McManus, M. T., Schwartz, R. J., Srivastava, D.
|
|
<strong>Dysregulation of cardiogenesis, cardiac conduction, and cell cycle in mice lacking miRNA-1-2.</strong>
|
|
Cell 129: 303-317, 2007.
|
|
|
|
|
|
[PubMed: 17397913]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cell.2007.03.030]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 01/04/2019<br>Cassandra L. Kniffin - updated : 11/08/2017<br>George E. Tiller - updated : 06/21/2017<br>Ada Hamosh - updated : 1/14/2015<br>Ada Hamosh - updated : 11/24/2014<br>Ada Hamosh - updated : 1/31/2014<br>Ada Hamosh - updated : 12/6/2013<br>Ada Hamosh - updated : 10/10/2013<br>Paul J. Converse - updated : 3/13/2013<br>Paul J. Converse - updated : 10/23/2012<br>Ada Hamosh - updated : 8/28/2012<br>Cassandra L. Kniffin - updated : 4/2/2012<br>Ada Hamosh - updated : 8/24/2011<br>Patricia A. Hartz - updated : 6/14/2011<br>Ada Hamosh - updated : 6/7/2011<br>Cassandra L. Kniffin - updated : 3/16/2011<br>Ada Hamosh - updated : 12/27/2010<br>Patricia A. Hartz - updated : 8/20/2010<br>Ada Hamosh - updated : 6/14/2010<br>Ada Hamosh - updated : 5/26/2010<br>Ada Hamosh - updated : 5/10/2010<br>Marla J. F. O'Neill - updated : 12/9/2009<br>Ada Hamosh - updated : 9/9/2009<br>Patricia A. Hartz - updated : 8/20/2009<br>Patricia A. Hartz - updated : 5/5/2009<br>Cassandra L. Kniffin - updated : 3/19/2009<br>Paul J. Converse - updated : 2/6/2009<br>Cassandra L. Kniffin - updated : 1/30/2009<br>Patricia A. Hartz - updated : 8/18/2008<br>Ada Hamosh - updated : 7/9/2008<br>Ada Hamosh - updated : 6/11/2008<br>Ada Hamosh - updated : 6/10/2008<br>Cassandra L. Kniffin - updated : 4/28/2008<br>Paul J. Converse - updated : 10/24/2007<br>Patricia A. Hartz - updated : 5/2/2007<br>Paul J. Converse - updated : 12/6/2006<br>Patricia A. Hartz - updated : 7/28/2006<br>Ada Hamosh - updated : 5/15/2006<br>Ada Hamosh - updated : 4/25/2006<br>Ada Hamosh - updated : 4/18/2006<br>Paul J. Converse - updated : 4/3/2006<br>Victor A. McKusick - updated : 3/6/2006<br>Patricia A. Hartz - updated : 2/10/2006<br>Ada Hamosh - updated : 9/7/2005<br>Stylianos E. Antonarakis - updated : 3/28/2005<br>Patricia A. Hartz - updated : 3/8/2005<br>Ada Hamosh - updated : 12/10/2004<br>Stylianos E. Antonarakis - updated : 8/3/2004<br>Victor A. McKusick - updated : 10/9/2003<br>Ada Hamosh - updated : 11/20/2002
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh : 8/31/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
carol : 01/15/2025<br>carol : 10/08/2019<br>carol : 08/26/2019<br>carol : 01/08/2019<br>alopez : 01/04/2019<br>alopez : 01/04/2019<br>alopez : 04/09/2018<br>carol : 01/17/2018<br>carol : 11/14/2017<br>carol : 11/13/2017<br>carol : 11/10/2017<br>ckniffin : 11/08/2017<br>alopez : 06/21/2017<br>alopez : 06/21/2017<br>joanna : 10/16/2016<br>carol : 10/05/2016<br>alopez : 10/02/2015<br>carol : 5/7/2015<br>alopez : 1/14/2015<br>alopez : 11/24/2014<br>alopez : 1/31/2014<br>alopez : 12/6/2013<br>alopez : 10/10/2013<br>alopez : 10/10/2013<br>carol : 9/16/2013<br>terry : 4/4/2013<br>mgross : 3/18/2013<br>mgross : 3/18/2013<br>terry : 3/13/2013<br>mgross : 2/5/2013<br>mgross : 11/21/2012<br>terry : 10/23/2012<br>alopez : 8/30/2012<br>terry : 8/28/2012<br>carol : 6/4/2012<br>carol : 4/4/2012<br>ckniffin : 4/2/2012<br>alopez : 8/25/2011<br>terry : 8/24/2011<br>mgross : 6/22/2011<br>terry : 6/14/2011<br>alopez : 6/14/2011<br>alopez : 6/14/2011<br>terry : 6/7/2011<br>terry : 3/25/2011<br>terry : 3/18/2011<br>terry : 3/18/2011<br>wwang : 3/17/2011<br>ckniffin : 3/16/2011<br>alopez : 1/5/2011<br>terry : 12/27/2010<br>mgross : 9/1/2010<br>terry : 8/20/2010<br>alopez : 6/21/2010<br>terry : 6/14/2010<br>alopez : 5/27/2010<br>alopez : 5/27/2010<br>terry : 5/26/2010<br>alopez : 5/10/2010<br>wwang : 12/11/2009<br>terry : 12/9/2009<br>alopez : 9/10/2009<br>terry : 9/9/2009<br>mgross : 8/25/2009<br>terry : 8/20/2009<br>mgross : 5/5/2009<br>wwang : 3/20/2009<br>ckniffin : 3/19/2009<br>mgross : 2/6/2009<br>mgross : 2/6/2009<br>carol : 2/6/2009<br>ckniffin : 1/30/2009<br>wwang : 10/6/2008<br>wwang : 8/22/2008<br>terry : 8/18/2008<br>wwang : 7/15/2008<br>terry : 7/9/2008<br>alopez : 6/11/2008<br>terry : 6/10/2008<br>wwang : 6/6/2008<br>ckniffin : 4/28/2008<br>mgross : 10/24/2007<br>wwang : 5/2/2007<br>wwang : 5/2/2007<br>mgross : 12/6/2006<br>wwang : 8/7/2006<br>terry : 7/28/2006<br>alopez : 5/23/2006<br>terry : 5/15/2006<br>alopez : 4/25/2006<br>terry : 4/25/2006<br>alopez : 4/21/2006<br>terry : 4/18/2006<br>mgross : 4/5/2006<br>terry : 4/3/2006<br>wwang : 3/29/2006<br>terry : 3/24/2006<br>alopez : 3/9/2006<br>terry : 3/6/2006<br>mgross : 3/1/2006<br>wwang : 2/10/2006<br>alopez : 9/14/2005<br>terry : 9/7/2005<br>mgross : 3/28/2005<br>mgross : 3/8/2005<br>alopez : 12/15/2004<br>terry : 12/10/2004<br>mgross : 8/3/2004<br>alopez : 1/16/2004<br>alopez : 10/31/2003<br>alopez : 10/14/2003<br>alopez : 10/13/2003<br>terry : 10/9/2003<br>cwells : 11/20/2002<br>terry : 11/18/2002<br>alopez : 8/31/2001
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 5, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|