4349 lines
439 KiB
Text
4349 lines
439 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
|
|
|
|
- *604610 - RECQ PROTEIN-LIKE 3; RECQL3
|
|
|
|
|
|
- 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=604610"><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>
|
|
</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">*604610</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="#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="#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="#geneFamily">Gene Family</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/604610">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=ENSG00000197299;t=ENST00000355112" 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=641" 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=604610" 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=ENSG00000197299;t=ENST00000355112" 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_000057,NM_001287246,NM_001287247,NM_001287248,XM_006720632,XM_011521882,XM_047432934" 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_000057" 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=604610" 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=05211&isoform_id=05211_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/BLM" 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/1072122,1705486,4557365,58003498,62739395,75517719,77567567,92096020,92097932,119622512,119622513,189054874,219518767,221040662,221044460,564730687,564730689,564730691,578827270,767984940,2178104979,2217302303,2462545467,2462545469,2462545471" 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/P54132" 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=641" 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=ENSG00000197299;t=ENST00000355112" 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=BLM" 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=BLM" 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+641" 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/BLM" 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:641" 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/641" 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=chr15&hgg_gene=ENST00000355112.8&hgg_start=90717346&hgg_end=90816166&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:1058" 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:1058" 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/blm" 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=604610[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=604610[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://gnomad.broadinstitute.org/gene/ENSG00000197299" 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=BLM" 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=BLM" 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=BLM" 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="http://structure.bmc.lu.se/idbase/BLMbase/index.php" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=BLM&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/PA25369" 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:1058" 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/FBgn0002906.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:1328362" 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/BLM#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:1328362" 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/641/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=641" 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=WBGene00001865;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-070702-5" 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="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:604610" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:641" 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=BLM&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> 4434006<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>
|
|
604610
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
RECQ PROTEIN-LIKE 3; RECQL3
|
|
|
|
</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">
|
|
DNA HELICASE, RECQ-LIKE, TYPE 2; RECQ2<br />
|
|
BLM GENE; BLM
|
|
</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=BLM" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">BLM</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/15/520?start=-3&limit=10&highlight=520">15q26.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:90717346-90816166&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'})">15:90,717,346-90,816,166</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
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/15/520?start=-3&limit=10&highlight=520">
|
|
15q26.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Bloom syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/210900"> 210900 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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>
|
|
|
|
|
|
</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/604610" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604610" 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 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<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 id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>The RecQ gene family is named after the E. coli gene. RecQ is an E. coli gene that is a member of the RecF recombination pathway, a pathway of genes in which mutations abolish the conjugational recombination proficiency and ultraviolet resistance of a mutant strain. RECQL (<a href="/entry/600537">600537</a>) is a human gene isolated from HeLa cells, the product of which possesses DNA-dependent ATPase, DNA helicase, and 3-prime-to-5-prime single-stranded DNA translocation activities.</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>The hypermutability of Bloom syndrome (BLM; <a href="/entry/210900">210900</a>) cells includes hyperrecombinability. <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> noted that although cells from all persons with Bloom syndrome exhibit the diagnostic high sister chromatid exchange (SCE) rate, in some persons a minor population of low SCE lymphocytes exist in the blood. Lymphoblastoid cell lines (LCLs) with low SCE rates can be developed from these low SCE lymphocytes. In multiple low SCE LCLs examined from 11 patients with BS, polymorphic loci distal to BLM on 15q had become homozygous in LCLs from 5 persons, whereas polymorphic loci proximal to the BLM locus remained heterozygous in all low SCE LCLs. These observations supported the hypothesis that low SCE lymphocytes arose through recombination within the BLM locus in persons with BS who had inherited paternally and maternally derived BLM alleles mutated at different sites. Such a recombination event in a precursor stem cell in these compound heterozygotes thus gave rise to a cell whose progeny had a functionally wildtype gene and phenotypically a low SCE rate (<a href="#10" class="mim-tip-reference" title="Ellis, N. A., Lennon, D. J., Proytcheva, M., Alhadeff, B., Henderson, E. E., German, J. <strong>Somatic intragenic recombination within the mutated locus BLM can correct the high SCE phenotype of Bloom syndrome cells.</strong> Am. J. Hum. Genet. 57: 1019-1027, 1995. Note: Erratum: Am. J. Hum. Genet. 58: 254 only, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7485150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7485150</a>]" pmid="7485150">Ellis et al., 1995</a>). <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> used the low SCE LCLs in which reduction to homozygosity had occurred for localizing BLM by an approach referred to as somatic crossover point (SCP) mapping. The precise map position of BLM was determined by comparing the genotypes of the recombinant low SCE LCLs from the 5 persons mentioned above with their constitutional genotypes at loci in the region around BLM. The strategy was to identify the most proximal polymorphic locus possible that was constitutionally heterozygous and that had been reduced to homozygosity in the low SCE LCLs, and to identify the most distal polymorphic locus possible that had remained constitutionally heterozygous in them. The BLM gene would have to be in the short interval defined by the reduced (distal) and the unreduced (proximal) heterozygous markers. The power of this approach was limited only by the density of polymorphic loci available in the immediate vicinity of BLM. A candidate for BLM was identified by direct selection of a cDNA derived from a 250-kb segment of the genome in 15q26.1 to which BLM had been assigned by SCP mapping. cDNA analysis of the candidate gene identified a 4,437-bp cDNA that encoded a 1,417-amino acid peptide with homology to the RecQ helicases, a subfamily of DExH box-containing DNA and RNA helicases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7585968+7485150" 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>The RECQL3 gene maps to chromosome 15q26.1 (<a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al., 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7585968" 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><a href="#8" class="mim-tip-reference" title="Ellis, N. A., German, J. <strong>Molecular genetics of Bloom's syndrome.</strong> Hum. Molec. Genet. 5: 1457-1463, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8875252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8875252</a>] [<a href="https://doi.org/10.1093/hmg/5.supplement_1.1457" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8875252">Ellis and German (1996)</a> reported that the BLM protein has similarity to 2 other proteins that are members of the RecQ family of helicases, namely the gene product encoded by RECQL2 (<a href="/entry/604611">604611</a>), also called WRN, and the product of the yeast gene Sgs1. Sgs1 was identified by a mutation that suppressed the slow-growth phenotype of mutations in the topoisomerase gene (see <a href="/entry/126420">126420</a>). These proteins have 42 to 44% amino acid identity across the conserved helicase motifs. In addition, the proteins are of similar length and contain highly negatively charged N-terminal regions and highly positively charged C-terminal regions. <a href="#8" class="mim-tip-reference" title="Ellis, N. A., German, J. <strong>Molecular genetics of Bloom's syndrome.</strong> Hum. Molec. Genet. 5: 1457-1463, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8875252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8875252</a>] [<a href="https://doi.org/10.1093/hmg/5.supplement_1.1457" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8875252">Ellis and German (1996)</a> noted that these similarities in overall structure have raised the possibility that the proteins play similar roles in metabolism. Since the Sgs1 gene product is known to interact with the products of the yeast topoisomerase genes, they predicted that the BLM and WRN genes interact with human topoisomerases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8875252" 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="#11" class="mim-tip-reference" title="Ellis, N. A., Proytcheva, M., Sanz, M. M., Ye, T.-Z., German, J. <strong>Transfection of BLM into cultured Bloom syndrome cells reduces the sister-chromatid exchange rate toward normal.</strong> Am. J. Hum. Genet. 65: 1368-1374, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10521302[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/10.1086/302616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10521302">Ellis et al. (1999)</a> described the effects on the abnormal cellular phenotype of BS, namely an excessive rate of SCE, when normal BLM cDNA was stably transfected into 2 types of BS cells, SV40-transformed fibroblasts and Epstein-Barr virus-transformed lymphoblastoid cells. The experiments proved that BLM cDNA encodes a functional protein capable of restoring to or toward normal the uniquely characteristic high-SCE phenotype of BS cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10521302" 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 an immunocytologic study of mouse spermatocytes, <a href="#36" class="mim-tip-reference" title="Walpita, D., Plug, A. W., Neff, N. F., German, J., Ashley, T. <strong>Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes.</strong> Proc. Nat. Acad. Sci. 96: 5622-5627, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10318934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10318934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10318934[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.96.10.5622" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10318934">Walpita et al. (1999)</a> showed that the BLM protein is first evident as discrete foci along the synaptonemal complexes of homologously synapsed autosomal bivalents in late zygonema of meiotic prophase. BLM foci progressively dissociated from the synapsed autosomal axes during early pachynema and were no longer seen in mid-pachynema. BLM colocalized with the single-stranded DNA-binding replication protein A (see <a href="/entry/179835">179835</a>), which had been shown to be involved in meiotic synapsis. However, there was a temporary delay in the appearance of BLM protein along the synaptonemal complexes relative to replication protein A, suggesting that BLM is required for a late step in processing of a subset of genomic DNA involved in establishment of interhomolog interactions in early meiotic prophase. In late pachynema and into diplonema, BLM is more dispersed in the nucleoplasm, especially over the chromatin most intimately associated with the synaptonemal complexes, suggesting a possible involvement of BLM in resolution of interlocks in preparation for homologous chromosome disjunction during anaphase I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10318934" 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="Yankiwski, V., Marciniak, R. A., Guarente, L., Neff, N. F. <strong>Nuclear structure in normal and Bloom syndrome cells.</strong> Proc. Nat. Acad. Sci. 97: 5214-5219, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10779560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10779560</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10779560[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.090525897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10779560">Yankiwski et al. (2000)</a> found that the BLM protein is located in the nucleus of normal human cells in the nuclear domain 10 (ND10; see <a href="/entry/604587">604587</a>) or promyelocytic leukemia nuclear bodies. These structures are punctate deposits of proteins disrupted upon viral infection and in certain human malignancies. BLM was found primarily in ND10 except during S phase, when it colocalized with the WRN gene product, in the nucleolus. BLM colocalized with a select subset of telomeres in normal cells and with large telomeric clusters seen in simian virus 40-transformed normal fibroblasts. During S phase, Bloom syndrome cells expel micronuclei containing sites of DNA synthesis. The BLM protein is likely to be part of a DNA surveillance mechanism operating during S phase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10779560" 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="#35" class="mim-tip-reference" title="von Kobbe, C., Karmakar, P., Dawut, L., Opresko, P., Zeng, X., Brosh, R. M., Jr., Hickson, I. D., Bohr, V. A. <strong>Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.</strong> J. Biol. Chem. 277: 22035-22044, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11919194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11919194</a>] [<a href="https://doi.org/10.1074/jbc.M200914200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11919194">Von Kobbe et al. (2002)</a> confirmed interaction between BLM and WRN in immunoprecipitates of soluble nuclear extracts of HeLa cells. Immunolocalization of endogenous BLM and exogenously expressed WRN in several human cell lines showed colocalization of the 2 helicases in some nuclear foci and not in others, suggesting that their interaction is dynamic. Using pull-down assays with several truncation mutants, <a href="#35" class="mim-tip-reference" title="von Kobbe, C., Karmakar, P., Dawut, L., Opresko, P., Zeng, X., Brosh, R. M., Jr., Hickson, I. D., Bohr, V. A. <strong>Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.</strong> J. Biol. Chem. 277: 22035-22044, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11919194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11919194</a>] [<a href="https://doi.org/10.1074/jbc.M200914200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11919194">von Kobbe et al. (2002)</a> determined that the BLM-binding regions of WRN include the N-terminal exonuclease domain and the RQC-containing regions. They mapped the WRN-binding region of BLM to the middle of the molecule. <a href="#35" class="mim-tip-reference" title="von Kobbe, C., Karmakar, P., Dawut, L., Opresko, P., Zeng, X., Brosh, R. M., Jr., Hickson, I. D., Bohr, V. A. <strong>Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.</strong> J. Biol. Chem. 277: 22035-22044, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11919194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11919194</a>] [<a href="https://doi.org/10.1074/jbc.M200914200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11919194">Von Kobbe et al. (2002)</a> showed that BLM, by binding the exonuclease domain of WRN, inhibited WRN exonuclease activity. BLM had no effect on WRN helicase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11919194" 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>Bloom syndrome cells show marked genomic instability; in particular, hyperrecombination between sister chromatids and homologous chromosomes. <a href="#23" class="mim-tip-reference" title="Karow, J. K., Constantinou, A., Li, J.-L., West, S. C., Hickson, I. D. <strong>The Bloom's syndrome gene product promotes branch migration of Holliday junctions.</strong> Proc. Nat. Acad. Sci. 97: 6504-6508, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10823897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10823897</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10823897[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.100448097" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10823897">Karow et al. (2000)</a> investigated the mechanism by which the BLM protein normally suppresses hyperrecombination. They showed that in vitro BLM selectively binds Holliday junctions formed during genetic recombination and acts on recombination intermediates containing a Holliday junction to promote ATP-dependent branch migration. They presented a model in which BLM disrupts potentially recombinogenic molecules that arise at sites of stalled replication forks. They suggested that their results have implications for the role of BLM as an antirecombinase in the suppression of tumorigenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10823897" 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 various truncations of the BLM protein attached to green fluorescent protein, <a href="#22" class="mim-tip-reference" title="Kaneko, H., Orii, K. O., Matsui, E., Shimozawa, N., Fukao, T., Matsumoto, T., Shimamoto, A., Furuichi, Y., Hayakawa, S., Kasahara, K., Kondo, N. <strong>BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal.</strong> Biochem. Biophys. Res. Commun. 240: 348-353, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9388480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9388480</a>] [<a href="https://doi.org/10.1006/bbrc.1997.7648" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9388480">Kaneko et al. (1997)</a> found that only the BLM protein truncated at amino acid 1357, containing an intact helicase domain and 2 arms, was transported to the nucleus, indicating that BLM protein translocates into the nucleus and that the distal arm of the bipartite basic residues in the C terminus of the BLM protein is essential for targeting the nucleus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9388480" 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="Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., Qin, J. <strong>BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.</strong> Genes Dev. 14: 927-939, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10783165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10783165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10783165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="10783165">Wang et al. (2000)</a> used immunoprecipitation and mass spectrometry analyses to identify BRCA1 (<a href="/entry/113705">113705</a>)-associated proteins. They found that BRCA1 is part of a large multisubunit protein complex of tumor suppressors, DNA damage sensors, and signal transducers. They named this complex BASC, for 'BRCA1-associated genome surveillance complex.' Among the DNA repair proteins identified in the complex were ATM (<a href="/entry/607585">607585</a>), BLM, MSH2 (<a href="/entry/609309">609309</a>), MSH6 (<a href="/entry/600678">600678</a>), MLH1 (<a href="/entry/120436">120436</a>), the RAD50 (<a href="/entry/604040">604040</a>)-MRE11 (<a href="/entry/600814">600814</a>)-NBS1 (<a href="/entry/602667">602667</a>) complex, and the RFC1 (<a href="/entry/102579">102579</a>)-RFC2 (<a href="/entry/600404">600404</a>)-RFC4 (<a href="/entry/102577">102577</a>) complex. Confocal microscopy demonstrated that BRCA1, BLM, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci. <a href="#38" class="mim-tip-reference" title="Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., Qin, J. <strong>BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.</strong> Genes Dev. 14: 927-939, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10783165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10783165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10783165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="10783165">Wang et al. (2000)</a> suggested that BASC may serve as a sensor of abnormal DNA structures and/or as a regulator of the postreplication repair process. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10783165" 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 coimmunoprecipitation and in vitro pull-down assays, <a href="#3" class="mim-tip-reference" title="Beamish, H., Kedar, P., Kaneko, H., Chen, P., Fukao, T., Peng, C., Beresten, S., Gueven, N., Purdie, D., Lees-Miller, S., Ellis, N., Kondo, N., Lavin, M. F. <strong>Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM.</strong> J. Biol. Chem. 277: 30515-30523, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034743</a>] [<a href="https://doi.org/10.1074/jbc.M203801200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12034743">Beamish et al. (2002)</a> verified direct interaction between ATM and BLM. By mutation analysis, they mapped the BLM-binding domain of ATM to residues 82 through 89. The ATM-binding region of BLM mapped to residues 636 to 1,074. <a href="#3" class="mim-tip-reference" title="Beamish, H., Kedar, P., Kaneko, H., Chen, P., Fukao, T., Peng, C., Beresten, S., Gueven, N., Purdie, D., Lees-Miller, S., Ellis, N., Kondo, N., Lavin, M. F. <strong>Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM.</strong> J. Biol. Chem. 277: 30515-30523, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034743</a>] [<a href="https://doi.org/10.1074/jbc.M203801200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12034743">Beamish et al. (2002)</a> determined that the mitosis-associated hyperphosphorylation of BLM was partially dependent upon ATM phosphorylating thr99 and thr122 in the N-terminal region of BLM. Radiation-induced phosphorylation of BLM at thr99 was dose-dependent in normal cells and was defective in AT cells. BS lymphoblasts showed radiosensitivity that could be corrected by transfection of wildtype BLM but not by transfection of a thr99 phosphorylation-minus mutant. This phosphorylation-minus mutant did not alter SCE frequency, indicating that radiosensitivity and increased SCE are mediated by separate BLM domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12034743" 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="Wu, L., Davies, S. L., North, P. S., Goulaouic, H., Riou, J.-F., Turley, H., Gatter, K. C., Hickson, I. D. <strong>The Bloom's syndrome gene product interacts with topoisomerase III.</strong> J. Biol. Chem. 275: 9636-9644, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10734115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10734115</a>] [<a href="https://doi.org/10.1074/jbc.275.13.9636" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10734115">Wu et al. (2000)</a> determined that BLM and topoisomerase III-alpha (TOP3A; <a href="/entry/601243">601243</a>) colocalized in the nucleus of human cells and coimmunoprecipitated from cell extracts. By in vitro binding assays with truncated BLM mutants, the authors identified 2 independent domains that mediate the interaction with TOP3A. One domain resides between residues 143 and 212 in the N-terminal domain of BLM, and the other resides between residues 1266 and 1417 in the C-terminal domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10734115" 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="#5" class="mim-tip-reference" title="Dutertre, S., Sekhri, R., Tintignac, L. A., Onclercq-Delic, R., Chatton, B., Jaulin, C., Amor-Gueret, M. <strong>Dephosphorylation and subcellular compartment change of the mitotic Bloom's syndrome DNA helicase in response to ionizing radiation.</strong> J. Biol. Chem. 277: 6280-6286, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741924</a>] [<a href="https://doi.org/10.1074/jbc.M105735200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11741924">Dutertre et al. (2002)</a> noted that BLM is phosphorylated and is excluded from the nuclear matrix during mitosis. BLM immunopurified from mitosis-arrested HeLa cells was phosphorylated and showed 3-prime-to-5-prime DNA helicase activity. Coimmunoprecipitation experiments revealed that phosphorylated BLM interacted with TOP3A. BLM was dephosphorylated in response to ionizing radiation and by inhibition of CDC2 (<a href="/entry/116940">116940</a>)/cyclin B (<a href="/entry/123836">123836</a>). Upon dephosphorylation, BLM relocalized to an insoluble subcellular compartment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741924" 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="#30" class="mim-tip-reference" title="Mohaghegh, P., Hickson, I. D. <strong>DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders.</strong> Hum. Molec. Genet. 10: 741-746, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11257107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11257107</a>] [<a href="https://doi.org/10.1093/hmg/10.7.741" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11257107">Mohaghegh and Hickson (2001)</a> reviewed the DNA helicase deficiencies associated with cancer predisposition and premature aging disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11257107" 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="Opresko, P. L., von Kobbe, C., Laine, J.-P., Harrigan, J., Hickson, I. D., Bohr, V. A. <strong>Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.</strong> J. Biol. Chem. 277: 41110-41119, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12181313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12181313</a>] [<a href="https://doi.org/10.1074/jbc.M205396200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12181313">Opresko et al. (2002)</a> found that, in vitro, TRF2 (<a href="/entry/602027">602027</a>) showed high affinity for BLM and for WRN, and that TRF2 interaction with either helicase resulted in stimulation of its activity. WRN or BLM, partnered with replication protein A (RPA; see <a href="/entry/179835">179835</a>), actively unwound long telomeric duplex regions that were pre-bound by TRF2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12181313" 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>Telomerase-negative immortalized human cells maintain telomeres by alternative lengthening of telomeres (ALT) pathway(s), which may involve homologous recombination. <a href="#33" class="mim-tip-reference" title="Stavropoulos, D. J., Bradshaw, P. S., Li, X., Pasic, I., Truong, K., Ikura, M., Ungrin, M., Meyn, M. S. <strong>The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.</strong> Hum. Molec. Genet. 11: 3135-3144, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12444098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12444098</a>] [<a href="https://doi.org/10.1093/hmg/11.25.3135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12444098">Stavropoulos et al. (2002)</a> found that endogenous BLM protein colocalized with telomeric foci in ALT human cells but not telomerase-positive immortal cell lines or primary cells. BLM interacted in vivo with the telomeric protein TRF2 in ALT cells, as detected by FRET and coimmunoprecipitation. Transient overexpression of GFP-BLM resulted in marked, ALT cell-specific increases in telomeric DNA. The association of BLM with telomeres and its effect on telomere DNA synthesis required a functional helicase domain. The authors suggested that BLM may facilitate recombination-driven amplification of telomeres in ALT cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12444098" 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="#14" class="mim-tip-reference" title="Franchitto, A., Pichierri, P. <strong>Protecting genomic integrity during DNA replication: correlation between Werner's and Bloom's syndrome gene products and the MRE11 complex.</strong> Hum. Molec. Genet. 11: 2447-2453, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351580</a>] [<a href="https://doi.org/10.1093/hmg/11.20.2447" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12351580">Franchitto and Pichierri (2002)</a> reviewed the roles of RECQL2 and RECQL3 in resolution of a stall in DNA replication, as well as their possible interaction with the MRE11-RAD50-NBS1 complex. Components of this complex are mutated in 2 genetic instability syndromes, Nijmegen breakage syndrome (<a href="/entry/251260">251260</a>) and ataxia telangiectasia-like disorder (<a href="/entry/604391">604391</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12351580" 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="#21" class="mim-tip-reference" title="Imamura, O., Campbell, J. L. <strong>The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.</strong> Proc. Nat. Acad. Sci. 100: 8193-8198, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12826610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12826610</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12826610[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.1431624100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12826610">Imamura and Campbell (2003)</a> showed that the human BLM gene can suppress both the temperature-sensitive growth defect and the DNA damage sensitivity of the yeast DNA replication mutant Dna2-1. This yeast mutant is defective in a helicase/nuclease that is required either to coordinate with the crucial Fen1 nuclease of the yeast in Okazaki fragment maturation or to compensate for yeast Fen1 when its activity is impaired. Using coimmunoprecipitation from yeast extracts, <a href="#21" class="mim-tip-reference" title="Imamura, O., Campbell, J. L. <strong>The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.</strong> Proc. Nat. Acad. Sci. 100: 8193-8198, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12826610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12826610</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12826610[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.1431624100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12826610">Imamura and Campbell (2003)</a> showed that human BLM interacts with both Dna2 and Fen1 of S. cerevisiae, suggesting that it participates in the same steps of DNA replication or repair as these 2 yeast proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12826610" 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="Wu, L., Hickson, I. D. <strong>The Bloom's syndrome helicase suppresses crossing over during homologous recombination.</strong> Nature 426: 870-874, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14685245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14685245</a>] [<a href="https://doi.org/10.1038/nature02253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14685245">Wu and Hickson (2003)</a> demonstrated that BLM and TOP3A together effect the resolution of a recombination intermediate containing a double Holliday junction. The mechanism, which they termed double-junction dissolution, is distinct from classical Holliday junction resolution and prevents exchange of flanking sequences. Loss of such an activity explains many of the cellular phenotypes of Bloom syndrome. <a href="#41" class="mim-tip-reference" title="Wu, L., Hickson, I. D. <strong>The Bloom's syndrome helicase suppresses crossing over during homologous recombination.</strong> Nature 426: 870-874, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14685245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14685245</a>] [<a href="https://doi.org/10.1038/nature02253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14685245">Wu and Hickson (2003)</a> proposed that double Holliday junctions are formed during the homologous recombination-dependent repair of daughter strand gaps that arise during replication, and that the dissolution of these double Holliday junctions by BLM prevents the diagnostically high sister chromatid exchange frequency seen in Bloom syndrome cells. Furthermore, BLM-catalyzed double-junction dissolution may act to suppress tumorigenesis by preventing loss of heterozygosity, a feature associated with BLM deficiency in mice, through the suppression of ectopic recombination and crossing-over between homologous chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14685245" 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 coimmunoprecipitation of HeLa cell nuclear extracts, <a href="#28" class="mim-tip-reference" title="Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E., Wang, W. <strong>A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.</strong> Molec. Cell. Biol. 23: 3417-3426, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12724401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12724401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12724401[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/10.1128/MCB.23.10.3417-3426.2003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12724401">Meetei et al. (2003)</a> identified 3 distinct multiprotein complexes associated with BLM, all of which were different from the BASC complex reported by <a href="#38" class="mim-tip-reference" title="Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., Qin, J. <strong>BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.</strong> Genes Dev. 14: 927-939, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10783165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10783165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10783165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="10783165">Wang et al. (2000)</a>. One of the complexes, designated BRAFT, contained the Fanconi anemia core complementation group proteins FANCA (<a href="/entry/607139">607139</a>), FANCG (<a href="/entry/602956">602956</a>), FANCC (<a href="/entry/613899">613899</a>), FANCE (<a href="/entry/613976">613976</a>), and FANCF (<a href="/entry/613897">613897</a>), as well as Topo III-alpha and RPA. BLM complexes isolated from an FA cell line had a lower molecular mass, likely due to loss of FANCA and other FA components. BLM- and FANCA-associated complexes had DNA unwinding activity, and BLM was required for this activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12724401+10783165" 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="#26" class="mim-tip-reference" title="Lillard-Wetherell, K., Machwe, A., Langland, G. T., Combs, K. A., Behbehani, G. K., Schonberg, S. A., German, J., Turchi, J. J., Orren, D. K., Groden, J. <strong>Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2.</strong> Hum. Molec. Genet. 13: 1919-1932, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15229185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15229185</a>] [<a href="https://doi.org/10.1093/hmg/ddh193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15229185">Lillard-Wetherell et al. (2004)</a> reported that BLM colocalized and complexed with TERF2 (<a href="/entry/602027">602027</a>) in cells that employ ALT. BLM colocalized with TERF2 in foci actively synthesizing DNA during late S and G2/M; colocalization increased in late S and G2/M when ALT is thought to occur. TERF1 (<a href="/entry/600951">600951</a>) and TERF2 interacted directly with BLM and regulated its unwinding activity in vitro. Whereas TERF2 stimulated BLM unwinding of telomeric and nontelomeric substrates, TERF1 inhibited its unwinding of telomeric substrates only. TERF2 stimulated BLM unwinding with equimolar concentrations of TERF1 but not when TRF1 was added in molar excess. <a href="#26" class="mim-tip-reference" title="Lillard-Wetherell, K., Machwe, A., Langland, G. T., Combs, K. A., Behbehani, G. K., Schonberg, S. A., German, J., Turchi, J. J., Orren, D. K., Groden, J. <strong>Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2.</strong> Hum. Molec. Genet. 13: 1919-1932, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15229185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15229185</a>] [<a href="https://doi.org/10.1093/hmg/ddh193" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15229185">Lillard-Wetherell et al. (2004)</a> proposed a function for BLM in recombination-mediated telomere lengthening and a model for the coordinated regulation of BLM activity at telomeres by TERF1 and TERF2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15229185" 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="Eladad, S., Ye, T.-Z., Hu, P., Leversha, M., Beresten, S., Matunis, M. J., Ellis, N. A. <strong>Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification.</strong> Hum. Molec. Genet. 14: 1351-1365, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829507</a>] [<a href="https://doi.org/10.1093/hmg/ddi145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15829507">Eladad et al. (2005)</a> showed that BLM is a substrate for SUMO1 (<a href="/entry/601912">601912</a>) modification, with lys317, lys331, lys334, and lys347 being preferred sites of modification. Unlike normal BLM, a double-mutant BLM protein with lysine-to-arginine substitutions at residues 317 and 331 was not modified by SUMO1, and it failed to localize efficiently to the PML nuclear bodies. Rather, double-mutant BLM protein induced the formation of DNA damage-induced foci (DDI) that contained BRCA1 (<a href="/entry/113705">113705</a>) protein and phosphorylated histone H2AX (<a href="/entry/601772">601772</a>). Double-mutant BLM only partially complemented the genomic instability phenotypes of Bloom syndrome cells as assessed by sister-chromatid exchange and micronuclei formation assays. <a href="#6" class="mim-tip-reference" title="Eladad, S., Ye, T.-Z., Hu, P., Leversha, M., Beresten, S., Matunis, M. J., Ellis, N. A. <strong>Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification.</strong> Hum. Molec. Genet. 14: 1351-1365, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829507</a>] [<a href="https://doi.org/10.1093/hmg/ddi145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15829507">Eladad et al. (2005)</a> hypothesized that BLM is a DNA damage sensor that signals the formation of DDI, for which SUMO1 modification is a negative regulator of BLM signaling function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15829507" 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="Mimitou, E. P., Symington, L. S. <strong>Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.</strong> Nature 455: 770-774, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18806779[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/nature07312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18806779">Mimitou and Symington (2008)</a> demonstrated that yeast Exo1 nuclease (<a href="/entry/606063">606063</a>) and Sgs1 helicase functioned in alternative pathways for double-strand break (DSB) processing. Novel, partially resected intermediates, whose initial generation depended on Sae2 (see <a href="/entry/604124">604124</a>), accumulated in yeast lacking both Exo1 and Sgs1 and were poor substrates for homologous recombination. When Sae2 was absent, in addition to Exo1 and Sgs1, homology-dependent repair failed and unprocessed DSBs accumulated. <a href="#29" class="mim-tip-reference" title="Mimitou, E. P., Symington, L. S. <strong>Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.</strong> Nature 455: 770-774, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18806779[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/nature07312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18806779">Mimitou and Symington (2008)</a> concluded that there is a 2-step mechanism for DSB processing during homologous recombination, with the Mre11 complex and Sae2 removing a small oligonucleotide from DNA ends to form an early intermediate, followed by processing of this intermediate by Exo1 and/or Sgs1 to generate extensive tracts of single-stranded DNA that serve as a substrate for Rad51 (<a href="/entry/179617">179617</a>). Since BLM is the human homolog of Sgs1, the results suggested that some of the defects observed in Bloom syndrome could be due to altered DSB processing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18806779" 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="#24" class="mim-tip-reference" title="Killen, M. W., Stults, D. M., Adachi, N., Hanakahi, L., Pierce, A. J. <strong>Loss of Bloom syndrome protein destabilizes human gene cluster architecture.</strong> Hum. Molec. Genet. 18: 3417-3428, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19542097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19542097</a>] [<a href="https://doi.org/10.1093/hmg/ddp282" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19542097">Killen et al. (2009)</a> used physical analysis of the highly repeated, self-similar ribosomal RNA gene clusters as sentinel biomarkers for dysregulated homologous recombination to demonstrate that loss of BLM protein function caused a striking increase in spontaneous molecular-level genomic restructuring. Analysis of single cell-derived subclonal populations from wildtype human cell lines showed that gene cluster architecture is ordinarily faithfully preserved under mitosis, but was so unstable in cell lines derived from BLMs as to make gene cluster architecture in different subclonal populations unrecognizable one from another. Cells defective in a different RecQ helicase, the WRN (RECQL2; <a href="/entry/604611">604611</a>) protein, did not exhibit the gene cluster instability (GCI) phenotype, indicating that the BLM protein specifically, rather than RecQ helicases generally, held back this recombination-mediated genomic instability. An ATM (<a href="/entry/607585">607585</a>)-defective cell line also showed elevated rDNA GCI, although not to the extent of BLM-defective cells. <a href="#24" class="mim-tip-reference" title="Killen, M. W., Stults, D. M., Adachi, N., Hanakahi, L., Pierce, A. J. <strong>Loss of Bloom syndrome protein destabilizes human gene cluster architecture.</strong> Hum. Molec. Genet. 18: 3417-3428, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19542097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19542097</a>] [<a href="https://doi.org/10.1093/hmg/ddp282" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19542097">Killen et al. (2009)</a> hypothesized that genomic restructuring mediated by dysregulated recombination between the abundant low-copy repeats in the human genome may be an important additional mechanism of genomic instability driving the initiation and progression of human cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19542097" 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="#39" class="mim-tip-reference" title="Wechsler, T., Newman, S., West, S. C. <strong>Aberrant chromosome morphology in human cells defective for Holliday junction resolution.</strong> Nature 471: 642-646, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21399624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21399624</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21399624[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/nature09790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21399624">Wechsler et al. (2011)</a> used Bloom syndrome cells, in which the BLM gene is inactive, to analyze human cells compromised for the known Holliday junction dissolution/resolution pathways. <a href="#39" class="mim-tip-reference" title="Wechsler, T., Newman, S., West, S. C. <strong>Aberrant chromosome morphology in human cells defective for Holliday junction resolution.</strong> Nature 471: 642-646, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21399624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21399624</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21399624[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/nature09790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21399624">Wechsler et al. (2011)</a> showed that depletion of MUS81 (<a href="/entry/606591">606591</a>) and GEN1 (<a href="/entry/612449">612449</a>), or SLX4 (<a href="/entry/613278">613278</a>) and GEN1, from Bloom syndrome cells results in severe chromosome abnormalities, such that sister chromatids remain interlinked in a side-by-side arrangement and the chromosomes are elongated and segmented. <a href="#39" class="mim-tip-reference" title="Wechsler, T., Newman, S., West, S. C. <strong>Aberrant chromosome morphology in human cells defective for Holliday junction resolution.</strong> Nature 471: 642-646, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21399624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21399624</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21399624[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/nature09790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21399624">Wechsler et al. (2011)</a> concluded that normally replicating human cells require Holliday junction processing activities to prevent sister chromatid entanglements and thereby ensure accurate chromosome condensation. This phenotype was not apparent when both MUS81 and SLX4 were depleted from Bloom syndrome cells, suggesting that GEN1 can compensate for their absence. Additionally, <a href="#39" class="mim-tip-reference" title="Wechsler, T., Newman, S., West, S. C. <strong>Aberrant chromosome morphology in human cells defective for Holliday junction resolution.</strong> Nature 471: 642-646, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21399624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21399624</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21399624[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/nature09790" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21399624">Wechsler et al. (2011)</a> showed that depletion of MUS81 or SLX4 reduces the high frequency of sister chromatid exchanges in Bloom syndrome cells, indicating that MUS81 and SLX4 promote sister chromatid exchange formation, in events that may ultimately drive the chromosome instabilities that underpin early-onset cancers associated with Bloom syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21399624" 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 protein interaction assays with human cell lines and expression constructs, <a href="#37" class="mim-tip-reference" title="Wan, L., Han, J., Liu, T., Dong, S., Xie, F., Chen, H., Huang, J. <strong>Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.</strong> Proc. Nat. Acad. Sci. 110: 10646-10651, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23509288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23509288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23509288[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.1220921110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23509288">Wan et al. (2013)</a> showed that BLM interacted with endogenous SPIDR (<a href="/entry/615384">615384</a>), a nuclear scaffolding protein. Both proteins colocalized to nuclear foci following DNA damage in HeLa cells. Knockdown of SPIDR or BLM via small interfering RNA resulted in increased frequency of sister chromatid exchange following DNA damage and impaired RAD51 focus formation. Coimmunoprecipitation experiments showed that BLM interacted in a ternary complex with SPIDR and RAD51. Knockdown of SPIDR in HeLa cells reduced the association of BLM with RAD51 and increased the number of chromosomal aberrations and cell sensitivity to DNA damage. <a href="#37" class="mim-tip-reference" title="Wan, L., Han, J., Liu, T., Dong, S., Xie, F., Chen, H., Huang, J. <strong>Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.</strong> Proc. Nat. Acad. Sci. 110: 10646-10651, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23509288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23509288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23509288[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.1220921110" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23509288">Wan et al. (2013)</a> concluded that SPIDR provides a link between BLM and the homologous recombination machinery. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23509288" 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="Hu, L., Kim, T. M., Son, M. Y., Kim, S.-A., Holland, C. L., Tateishi, S., Kim, D. H., Yew, P. R., Montagna, C., Dumitrache, L. C., Hasty, P. <strong>Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes.</strong> Nature 501: 569-572, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24013173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24013173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24013173[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/nature12500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24013173">Hu et al. (2013)</a> delineated 2 pathways that spontaneously fuse inverted repeats to generate unstable chromosomal rearrangements in wildtype mouse embryonic stem cells. Gamma radiation induced a RECQL3-regulated pathway that selectively fused identical, but not mismatched, repeats. By contrast, ultraviolet light induced a RAD18 (<a href="/entry/605256">605256</a>)-dependent pathway that efficiently fused mismatched repeats. In addition, TREX2 (<a href="/entry/300370">300370</a>), a 3-prime-to-5-prime exonuclease, suppressed identical repeat fusion but enhanced mismatched repeat fusion, clearly separating these pathways. TREX2 associated with UBC13 (<a href="/entry/603679">603679</a>) and enhanced PCNA (<a href="/entry/176740">176740</a>) ubiquitination in response to ultraviolet light, consistent with its being a novel member of error-free postreplication repair. RAD18 and TREX2 also suppressed replication fork stalling in response to nucleotide depletion. Replication fork stalling induced fusion for identical and mismatched repeats, implicating faulty replication as a causal mechanism for both pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24013173" 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>In patients with Bloom syndrome, <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> identified chain-terminating mutations in the BLM gene. Mutation analysis in the first 13 unrelated persons with BS examined permitted the identification of 7 unique mutations in 10 of them. The fact that 4 of the 7 mutations resulted in premature termination of translation indicated that the cause of most Bloom syndrome is the loss of enzymatic activity of the BLM gene product. Identification of loss-of-function mutations in BLM is consistent with the autosomal recessive transmission, and the homology of BLM and RecQ suggested that BLM has enzymatic activity. <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> suggested that the absence of the BLM gene product probably destabilizes other enzymes that participate in DNA replication and repair, perhaps through direct interaction and through more general responses to DNA damage. In 4 persons of Jewish ancestry, they detected a homozygous deletion/insertion mutation (<a href="#0001">604610.0001</a>) in the BLM gene. Homozygosity was predictable because linkage disequilibrium had been detected in Ashkenazi Jews with Bloom syndrome between BLM, D15S127, and FES (<a href="#12" class="mim-tip-reference" title="Ellis, N. A., Roe, A. M., Kozloski, J., Proytcheva, M., Falk, C., German, J. <strong>Linkage disequilibrium between the FES, D15S127, and BLM loci in Ashkenazi Jews with Bloom syndrome.</strong> Am. J. Hum. Genet. 55: 453-460, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8079989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8079989</a>]" pmid="8079989">Ellis et al., 1994</a>). Thus a person who carried this deletion/insertion mutation was a founder of Ashkenazi Jewish population and nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7585968+8079989" 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 a patient with Bloom syndrome and both high- and low-SCE cell lines, <a href="#13" class="mim-tip-reference" title="Foucault, F., Vaury, C., Barakat, A., Thibout, D., Planchon, P., Jaulin, C., Praz, F., Amor-Gueret, M. <strong>Characterization of a new BLM mutation associated with a topoisomerase II-alpha defect in a patient with Bloom's syndrome.</strong> Hum. Molec. Genet. 6: 1427-1434, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285778</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285778">Foucault et al. (1997)</a> identified compound heterozygosity for a cys1036-to-phe (C1036F; <a href="#0004">604610.0004</a>) substitution in the C-terminal region of the peptide and an unidentified mutation affecting expression of the RECQL3 gene. <a href="#13" class="mim-tip-reference" title="Foucault, F., Vaury, C., Barakat, A., Thibout, D., Planchon, P., Jaulin, C., Praz, F., Amor-Gueret, M. <strong>Characterization of a new BLM mutation associated with a topoisomerase II-alpha defect in a patient with Bloom's syndrome.</strong> Hum. Molec. Genet. 6: 1427-1434, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285778</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285778">Foucault et al. (1997)</a> concluded that somatic intragenic recombination resulted in cells that had an untranscribed allele carrying the 2 parental RECQL3 mutations and a wildtype allele which allowed reversion to the low SCE phenotype. Topoisomerase II-alpha (<a href="/entry/126430">126430</a>) mRNA and protein levels were decreased in the high SCE cells, whereas they were normal in the corresponding low SCE cells. <a href="#13" class="mim-tip-reference" title="Foucault, F., Vaury, C., Barakat, A., Thibout, D., Planchon, P., Jaulin, C., Praz, F., Amor-Gueret, M. <strong>Characterization of a new BLM mutation associated with a topoisomerase II-alpha defect in a patient with Bloom's syndrome.</strong> Hum. Molec. Genet. 6: 1427-1434, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285778</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285778">Foucault et al. (1997)</a> proposed that in addition to its putative helicase activity, RECQL3 might be involved in transcription regulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9285778" 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="German, J., Sanz, M. M., Ciocci, S., Ye, T. Z., Ellis, N. A. <strong>Syndrome-causing mutations of the BLM gene in persons in the Bloom's syndrome registry.</strong> Hum. Mutat. 28: 743-753, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17407155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17407155</a>] [<a href="https://doi.org/10.1002/humu.20501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17407155">German et al. (2007)</a> identified 64 different mutations in 125 of 134 individuals with Bloom syndrome from a patient registry. There were 54 mutations resulting in premature termination and 10 missense mutations. Several recurrent and founder mutations were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17407155" 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="geneFamily" class="mim-anchor"></a>
|
|
<h4 href="#mimGeneFamilyFold" id="mimGeneFamilyToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGeneFamilyToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Gene Family</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGeneFamilyFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>In their Table I, <a href="#27" class="mim-tip-reference" title="Lindor, N. M., Furuichi, Y., Kitao, S., Shimamoto, A., Arndt, C., Jalal, S. <strong>Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome.</strong> Am. J. Med. Genet. 90: 223-228, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10678659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10678659</a>] [<a href="https://doi.org/10.1002/(sici)1096-8628(20000131)90:3<223::aid-ajmg7>3.0.co;2-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10678659">Lindor et al. (2000)</a> provided a comparison of the 5 human RECQ helicases identified to that time. The RECQL3 gene is deficient in Bloom syndrome. The RECQL2 gene is deficient in Werner syndrome (<a href="/entry/277700">277700</a>), and the RECQL4 gene (<a href="/entry/603780">603780</a>) is deficient in Rothmund-Thomson syndrome (<a href="/entry/268400">268400</a>). No disorder had been related to RECQ1 (RECQL) or RECQL5 (<a href="/entry/603781">603781</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10678659" 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><a href="#4" class="mim-tip-reference" title="Chester, N., Kuo, F., Kozak, C., O'Hara, C. D., Leder, P. <strong>Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene.</strong> Genes Dev. 12: 3382-3393, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9808625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9808625</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9808625[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.12.21.3382" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9808625">Chester et al. (1998)</a> found that mouse embryos homozygous for a targeted mutation in the murine Bloom syndrome gene are developmentally delayed and die by embryonic day 13.5. They determined that the interrupted gene is the homolog of the human BLM gene by its homologous sequence, its chromosomal location, and the demonstration of high numbers of sister chromatid exchanges in cultured murine Blm -/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12 to 24 hours) seen during midgestation in murine Blm -/- embryos. The growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early postimplantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm -/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9808625" 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="#25" class="mim-tip-reference" title="Kusano, K., Johnson-Schlitz, D. M., Engels, W. R. <strong>Sterility of Drosophila with mutations in the Bloom syndrome gene--complementation by Ku70.</strong> Science 291: 2600-2602, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11283371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11283371</a>] [<a href="https://doi.org/10.1126/science.291.5513.2600" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11283371">Kusano et al. (2001)</a> demonstrated that Drosophila Dmblm is identical to mus309, a locus originally identified in a mutagen-sensitivity screen. One mus309 allele, which carries a stop codon between 2 of the helicase motifs, causes partial male sterility and complete female sterility. Mutant males produce an excess of XY sperm and nullo sperm, consistent with a high frequency of nondisjunction and/or chromosome loss. These phenotypes of mus309 suggest that Dmblm functions in DNA double-strand break repair. The mutant Dmblm phenotypes were partially rescued by an extra copy of the DNA repair gene Ku70 (<a href="/entry/152690">152690</a>), indicating that the 2 genes functionally interact in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11283371" 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="#17" class="mim-tip-reference" title="Goss, K. H., Risinger, M. A., Kordich, J. J., Sanz, M. M., Straughen, J. E., Slovek, L. E., Capobianco, A. J., German, J., Boivin, G. P., Groden, J. <strong>Enhanced tumor formation in mice heterozygous for Blm mutation.</strong> Science 297: 2051-2053, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242442</a>] [<a href="https://doi.org/10.1126/science.1074340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12242442">Goss et al. (2002)</a> used homologous recombination to disrupt the mouse Blm gene to simulate BLM(Ash), a frameshift mutation in the BLM gene present in 1% of Ashkenazi Jews. Mice heterozygous for this mutation developed lymphoma earlier than wildtype littermates in response to challenge with murine leukemia virus at birth and twice the number of intestinal tumors when crossed with mice carrying mutation in the APC gene (<a href="/entry/611731">611731</a>). <a href="#17" class="mim-tip-reference" title="Goss, K. H., Risinger, M. A., Kordich, J. J., Sanz, M. M., Straughen, J. E., Slovek, L. E., Capobianco, A. J., German, J., Boivin, G. P., Groden, J. <strong>Enhanced tumor formation in mice heterozygous for Blm mutation.</strong> Science 297: 2051-2053, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242442</a>] [<a href="https://doi.org/10.1126/science.1074340" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12242442">Goss et al. (2002)</a> concluded that Blm is a modifier of tumor formation in the mouse and that Blm haploinsufficiency is associated with tumor predisposition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12242442" 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="Adams, M. D., McVey, M., Sekelsky, J. J. <strong>Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing.</strong> Science 299: 265-267, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522255</a>] [<a href="https://doi.org/10.1126/science.1077198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12522255">Adams et al. (2003)</a> studied the Drosophila BLM ortholog MUS309 and demonstrated that mutants are severely impaired in their ability to carry out repair DNA synthesis during synthesis-dependent strand annealing. Consequently, repair in the mutants is completed by error-prone pathways that create large deletions. <a href="#1" class="mim-tip-reference" title="Adams, M. D., McVey, M., Sekelsky, J. J. <strong>Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing.</strong> Science 299: 265-267, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522255</a>] [<a href="https://doi.org/10.1126/science.1077198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12522255">Adams et al. (2003)</a> concluded that their results suggested a model in which BLM maintains genomic stability by promoting efficient repair DNA synthesis and thereby prevents double-strand break repair by less precise pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12522255" 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="Guo, G., Wang, W., Bradley, A. <strong>Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells.</strong> Nature 429: 891-895, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215866</a>] [<a href="https://doi.org/10.1038/nature02653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15215866">Guo et al. (2004)</a> exploited the high rate of mitotic recombination in Bloom syndrome protein (Blm)-deficient embryonic stem cells to generate a genomewide library of homozygous mutant cells from heterozygous mutations induced with a revertible gene trap retrovirus. <a href="#19" class="mim-tip-reference" title="Guo, G., Wang, W., Bradley, A. <strong>Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells.</strong> Nature 429: 891-895, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215866</a>] [<a href="https://doi.org/10.1038/nature02653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15215866">Guo et al. (2004)</a> screened this library for cells with defects in DNA mismatch repair (MMR), a system that detects and repairs base-base mismatches. They demonstrated the recovery of cells with homozygous mutations in known and novel mismatch repair genes. <a href="#19" class="mim-tip-reference" title="Guo, G., Wang, W., Bradley, A. <strong>Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells.</strong> Nature 429: 891-895, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215866</a>] [<a href="https://doi.org/10.1038/nature02653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15215866">Guo et al. (2004)</a> identified DNMT1 (<a href="/entry/126375">126375</a>) as a novel MMR gene and confirmed that Dnmt1-deficient embryonic stem cells exhibit microsatellite instability, providing a mechanistic explanation for the role of DNMT1 in cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15215866" 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="#43" class="mim-tip-reference" title="Yusa, K., Horie, K., Kondoh, G., Kouno, M., Maeda, Y., Kinoshita, T., Takeda, J. <strong>Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.</strong> Nature 429: 896-899, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215867</a>] [<a href="https://doi.org/10.1038/nature02646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15215867">Yusa et al. (2004)</a> used a tetracycline-regulated Blm allele, Blm(tet), to introduce biallelic mutations across the genome in mouse embryonic stem cells. Transient loss of Blm expression induced homologous recombination not only between sister chromatids but also between homologous chromosomes. <a href="#43" class="mim-tip-reference" title="Yusa, K., Horie, K., Kondoh, G., Kouno, M., Maeda, Y., Kinoshita, T., Takeda, J. <strong>Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.</strong> Nature 429: 896-899, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215867</a>] [<a href="https://doi.org/10.1038/nature02646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15215867">Yusa et al. (2004)</a> considered that the phenotype of embryonic stem cells bearing biallelic mutations would be maintained after withdrawal of the tetracycline analog doxycycline. Indeed, a combination of N-ethyl-N-nitrosourea mutagenesis and transient loss of Blm expression enabled them to generate an embryonic stem cell library with genomewide biallelic mutations. The library was evaluated by screening for mutants of glycosylphosphatidylinositol-anchor biosynthesis, which involves at least 23 genes distributed throughout the genome. Mutants derived from 12 different genes were obtained and 2 unknown mutants were simultaneously isolated. <a href="#43" class="mim-tip-reference" title="Yusa, K., Horie, K., Kondoh, G., Kouno, M., Maeda, Y., Kinoshita, T., Takeda, J. <strong>Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.</strong> Nature 429: 896-899, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215867</a>] [<a href="https://doi.org/10.1038/nature02646" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15215867">Yusa et al. (2004)</a> concluded that their results indicated that phenotype-based genetic screening with Blm(tet) is very efficient and raises possibilities for identifying gene functions in embryonic stem cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15215867" 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="Babbe, H., McMenamin, J., Hobeika, E., Wang, J., Rodig, S. J., Reth, M., Leder, P. <strong>Genomic instability resulting from Blm deficiency compromises development, maintenance, and function of the B cell lineage.</strong> J. Immun. 182: 347-360, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19109166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19109166</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19109166[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/10.4049/jimmunol.182.1.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19109166">Babbe et al. (2009)</a> found that specific inactivation of Blm in mouse B cells in vivo drastically reduced both developing B cells in bone marrow and mature B cells in the periphery, particularly the B1a subset. Serum concentrations of all Ig subtypes were low, even after immunization. Blm -/- B cells had reduced antibody class switch capacity in vitro, but Blm was not critical for class switch recombination. Mice with Blm -/- B cells that also lacked p53 (TP53; <a href="/entry/191170">191170</a>) had increased propensity to develop B-cell lymphoma due to high rates of chromosomal structural abnormalities and impaired cell cycle progression. <a href="#2" class="mim-tip-reference" title="Babbe, H., McMenamin, J., Hobeika, E., Wang, J., Rodig, S. J., Reth, M., Leder, P. <strong>Genomic instability resulting from Blm deficiency compromises development, maintenance, and function of the B cell lineage.</strong> J. Immun. 182: 347-360, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19109166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19109166</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19109166[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/10.4049/jimmunol.182.1.347" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19109166">Babbe et al. (2009)</a> concluded that BLM ensures proper development and function of the various B-cell subsets and also counteracts lymphomagenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19109166" 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>4 Selected Examples</a>):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimAllelicVariantsFold" class="collapse in mimTextToggleFold">
|
|
<div>
|
|
<a href="/allelicVariants/604610" class="btn btn-default" role="button"> Table View </a>
|
|
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=604610[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 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
BLM, 6-BP DEL/7-BP INS
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs113993962 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113993962;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs113993962?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs113993962" 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=rs113993962" 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=RCV000005787 OR RCV000058933 OR RCV000562115 OR RCV004745147" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005787, RCV000058933, RCV000562115, RCV004745147" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005787...</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 ostensibly unrelated persons of Jewish ancestry with Bloom syndrome (BLM; <a href="/entry/210900">210900</a>), <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> found homozygosity for a 6-bp deletion/7-bp insertion at nucleotide 2281 of the BLM cDNA. Deletion of ATCTGA and insertion of TAGATTC caused the insertion of the novel codons for LDSR after amino acid 736, and after these codons there was a stop codon. <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> concluded that a person carrying this deletion/insertion mutation was a founder of the Ashkenazi-Jewish population, and that nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. Identification of the mutation by a PCR test was now possible for screening for carriers among Ashkenazim. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7585968" 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="#34" class="mim-tip-reference" title="Straughen, J. E., Johnson, J., McLaren, D., Proytcheva, M., Ellis, N., German, J., Groden, J. <strong>A rapid method for detecting the predominant Ashkenazi Jewish mutation in the Bloom's syndrome gene.</strong> Hum. Mutat. 11: 175-178, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9482582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9482582</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)11:2<175::AID-HUMU11>3.0.CO;2-W" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9482582">Straughen et al. (1998)</a> described a rapid method for detecting the 6-bp deletion/7-bp insertion, a predominant Ashkenazi Jewish mutation in Bloom syndrome. They commented that in the Bloom syndrome registry, one or both parents of 52 of the 168 registered persons are Ashkenazi Jews. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9482582" 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 convenient PCR assay, <a href="#7" class="mim-tip-reference" title="Ellis, N. A., Ciocci, S., Proytcheva, M., Lennon, D., Groden, J., German, J. <strong>The Ashkenazic Jewish Bloom syndrome mutation blm(Ash) is present in non-Jewish Americans of Spanish ancestry.</strong> Am. J. Hum. Genet. 63: 1685-1693, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837821</a>] [<a href="https://doi.org/10.1086/302167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9837821">Ellis et al. (1998)</a> found the 6-bp del/7-bp ins mutation, blm(Ash), on 58 of 60 chromosomes transmitted by Ashkenazi parents to persons with Bloom syndrome. In contrast, in 91 unrelated non-Ashkenazic persons with BS whom they examined, blm(Ash) was identified in only 5, these coming from Spanish-speaking Christian families from the southwestern United States, Mexico, or El Salvador. These data, along with haplotype analyses, showed that blm(Ash) was independently established through a founder effect in Ashkenazi Jews and in immigrants to formerly Spanish colonies. This striking observation underscored the complexity of Jewish history and demonstrated the importance of migration and genetic drift in the formation of human populations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837821" 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 a study of the frequency of the BLM 6-bp del/7-bp ins mutation in a group of Ashkenazi Jews, unselected for personal or family history of Bloom syndrome, <a href="#31" class="mim-tip-reference" title="Oddoux, C., Clayton, C. M., Nelson, H. R., Ostrer, H. <strong>Prevalence of Bloom syndrome heterozygotes among Ashkenazi Jews. (Letter)</strong> Am. J. Hum. Genet. 64: 1241-1243, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10090915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10090915</a>] [<a href="https://doi.org/10.1086/302312" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10090915">Oddoux et al. (1999)</a> found the mutation in 5 of 1,155 individuals, yielding a frequency of 1/231 (95% CI, 1/123-1/1,848). The low frequency is consistent with an absence of heterozygote advantage for carriers of 1 copy of the mutant allele. The frequency of heterozygotes for other autosomal recessive conditions within their panel had been validated in other studies, suggesting that the test panel was representative of the Ashkenazi Jewish population. Those frequencies were Tay-Sachs disease, 1/28; cystic fibrosis, 1/25; Gaucher disease, 1/15; BRCA2, 6174delT, 1/106; Canavan disease, 1/41; and Fanconi anemia complementation group C, 1/116. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10090915" 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 determine whether carriers of BLM mutations are at increased risk of colorectal cancer, <a href="#18" class="mim-tip-reference" title="Gruber, S. B., Ellis, N. A., Scott, K. K., Almog, R., Kolachana, P., Bonner, J. D., Kirchhoff, T., Tomsho, L. P., Nafa, K., Pierce, H., Low, M., Satagopan, J., and 12 others. <strong>BLM heterozygosity and the risk of colorectal cancer.</strong> Science 297: 2013 only, 2002. Note: Erratum: Science 298: 751 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242432</a>] [<a href="https://doi.org/10.1126/science.1074399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12242432">Gruber et al. (2002)</a> genotyped 1,244 cases of colorectal cancer and 1,839 controls, both of Ashkenazi Jewish ancestry, to estimate the relative risk of colorectal cancer among carriers of the BLM(Ash) founder mutation. Ashkenazi Jews with colorectal cancer were more than twice as likely to carry the BLM(Ash) mutation than Ashkenazi Jewish controls without colorectal cancer (odds ratio = 2.45, 95% CI 1.3 to 4.8; P = 0.0065). <a href="#18" class="mim-tip-reference" title="Gruber, S. B., Ellis, N. A., Scott, K. K., Almog, R., Kolachana, P., Bonner, J. D., Kirchhoff, T., Tomsho, L. P., Nafa, K., Pierce, H., Low, M., Satagopan, J., and 12 others. <strong>BLM heterozygosity and the risk of colorectal cancer.</strong> Science 297: 2013 only, 2002. Note: Erratum: Science 298: 751 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242432</a>] [<a href="https://doi.org/10.1126/science.1074399" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12242432">Gruber et al. (2002)</a> verified that the APC I1307K mutation (<a href="/entry/611731#0029">611731.0029</a>) did not confound their results. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12242432" 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 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
BLM, 3-BP DEL, 631CAA
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs367543035 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs367543035;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=rs367543035" 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=rs367543035" 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=RCV000005788" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005788" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005788</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with Bloom syndrome (BLM; <a href="/entry/210900">210900</a>), <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> found homozygosity for a deletion of CAA at nucleotide position 631-633 in the BLM gene, resulting in a stop codon at amino acid position 186. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7585968" 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 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
BLM, EX11,12DEL
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000034895" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000034895" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000034895</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient (BSR92) with Bloom syndrome (BLM; <a href="/entry/210900">210900</a>), <a href="#16" class="mim-tip-reference" title="German, J., Sanz, M. M., Ciocci, S., Ye, T. Z., Ellis, N. A. <strong>Syndrome-causing mutations of the BLM gene in persons in the Bloom's syndrome registry.</strong> Hum. Mutat. 28: 743-753, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17407155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17407155</a>] [<a href="https://doi.org/10.1002/humu.20501" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17407155">German et al. (2007)</a> identified homozygosity for a large deletion in exons 11 and 12 in the RECQL3 gene (2308-953_2555+4719del6126), causing a frameshift (Ile770fs). (<a href="#15" class="mim-tip-reference" title="German, J., Ellis, N. <strong>Bloom syndrome. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. I. (8th ed.)</strong> New York: McGraw-Hill (pub.) 2001. P. 742."None>German and Ellis (2001)</a> noted that the mutation in patient BSR92 was assigned incorrectly by <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a>. <a href="#9" class="mim-tip-reference" title="Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J. <strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong> Cell 83: 655-666, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>] [<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7585968">Ellis et al. (1995)</a> had reported the patient to be homozygous for a 2596T-C transition resulting in an ile841-to-thr substitution. Table 1 in their article had erroneously stated that the change occurred at position 843.) <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7585968+17407155" 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 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
|
|
<div style="float: left;">
|
|
BLM, CYS1036PHE
|
|
</div>
|
|
|
|
</span>
|
|
|
|
|
|
|
|
<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853153 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853153;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=rs137853153" 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=rs137853153" 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=RCV000005790" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000005790" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000005790</a>
|
|
</span>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Bloom syndrome (BLM; <a href="/entry/210900">210900</a>), <a href="#13" class="mim-tip-reference" title="Foucault, F., Vaury, C., Barakat, A., Thibout, D., Planchon, P., Jaulin, C., Praz, F., Amor-Gueret, M. <strong>Characterization of a new BLM mutation associated with a topoisomerase II-alpha defect in a patient with Bloom's syndrome.</strong> Hum. Molec. Genet. 6: 1427-1434, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285778</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285778">Foucault et al. (1997)</a> identified compound heterozygosity for a 3181G-T transversion in the RECQL3 gene, resulting in a cys1036-to-phe (C1036F) substitution in the C-terminal region of the peptide, and an unidentified mutation affecting expression of the RECQL3 gene. The patient was initially believed to be homozygous for the C1036F mutation, but SSCP analysis, direct sequencing of RT-PCR products, and EcoRI digestion using a restriction site created by the mutation showed that the mutation was not present in low SCE cells from the patient. No EcoRI digestion was observed on paternal PCR products. Partial EcoRI digestion was seen with PCR products from maternal and patient DNA and from high- and low-SCE cells from the patient, and direct sequencing confirmed the presence of both a wildtype and mutated sequence at nucleotide 3181 in the high- and low-SCE cell lines, indicating heterozygosity for the mutation. <a href="#13" class="mim-tip-reference" title="Foucault, F., Vaury, C., Barakat, A., Thibout, D., Planchon, P., Jaulin, C., Praz, F., Amor-Gueret, M. <strong>Characterization of a new BLM mutation associated with a topoisomerase II-alpha defect in a patient with Bloom's syndrome.</strong> Hum. Molec. Genet. 6: 1427-1434, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285778</a>] [<a href="https://doi.org/10.1093/hmg/6.9.1427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9285778">Foucault et al. (1997)</a> concluded that somatic intragenic recombination resulted in cells that had an untranscribed allele carrying the 2 parental RECQL3 mutations and a wildtype allele which allowed reversion to the low-SCE phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9285778" 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="Adams2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Adams, M. D., McVey, M., Sekelsky, J. J.
|
|
<strong>Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing.</strong>
|
|
Science 299: 265-267, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12522255/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12522255</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12522255" 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.1077198" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Babbe2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Babbe, H., McMenamin, J., Hobeika, E., Wang, J., Rodig, S. J., Reth, M., Leder, P.
|
|
<strong>Genomic instability resulting from Blm deficiency compromises development, maintenance, and function of the B cell lineage.</strong>
|
|
J. Immun. 182: 347-360, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19109166/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19109166</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19109166[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=19109166" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.4049/jimmunol.182.1.347" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Beamish2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Beamish, H., Kedar, P., Kaneko, H., Chen, P., Fukao, T., Peng, C., Beresten, S., Gueven, N., Purdie, D., Lees-Miller, S., Ellis, N., Kondo, N., Lavin, M. F.
|
|
<strong>Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM.</strong>
|
|
J. Biol. Chem. 277: 30515-30523, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12034743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12034743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12034743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M203801200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Chester1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chester, N., Kuo, F., Kozak, C., O'Hara, C. D., Leder, P.
|
|
<strong>Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene.</strong>
|
|
Genes Dev. 12: 3382-3393, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9808625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9808625</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9808625[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=9808625" 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.12.21.3382" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Dutertre2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dutertre, S., Sekhri, R., Tintignac, L. A., Onclercq-Delic, R., Chatton, B., Jaulin, C., Amor-Gueret, M.
|
|
<strong>Dephosphorylation and subcellular compartment change of the mitotic Bloom's syndrome DNA helicase in response to ionizing radiation.</strong>
|
|
J. Biol. Chem. 277: 6280-6286, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11741924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11741924</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11741924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M105735200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Eladad2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eladad, S., Ye, T.-Z., Hu, P., Leversha, M., Beresten, S., Matunis, M. J., Ellis, N. A.
|
|
<strong>Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification.</strong>
|
|
Hum. Molec. Genet. 14: 1351-1365, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15829507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15829507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15829507" 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/ddi145" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Ellis1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Ciocci, S., Proytcheva, M., Lennon, D., Groden, J., German, J.
|
|
<strong>The Ashkenazic Jewish Bloom syndrome mutation blm(Ash) is present in non-Jewish Americans of Spanish ancestry.</strong>
|
|
Am. J. Hum. Genet. 63: 1685-1693, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9837821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9837821</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9837821" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302167" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Ellis1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., German, J.
|
|
<strong>Molecular genetics of Bloom's syndrome.</strong>
|
|
Hum. Molec. Genet. 5: 1457-1463, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8875252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8875252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8875252" 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/5.supplement_1.1457" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Ellis1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J.
|
|
<strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong>
|
|
Cell 83: 655-666, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7585968/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7585968</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7585968" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(95)90105-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Ellis1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Lennon, D. J., Proytcheva, M., Alhadeff, B., Henderson, E. E., German, J.
|
|
<strong>Somatic intragenic recombination within the mutated locus BLM can correct the high SCE phenotype of Bloom syndrome cells.</strong>
|
|
Am. J. Hum. Genet. 57: 1019-1027, 1995. Note: Erratum: Am. J. Hum. Genet. 58: 254 only, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7485150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7485150</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7485150" 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="11" class="mim-anchor"></a>
|
|
<a id="Ellis1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Proytcheva, M., Sanz, M. M., Ye, T.-Z., German, J.
|
|
<strong>Transfection of BLM into cultured Bloom syndrome cells reduces the sister-chromatid exchange rate toward normal.</strong>
|
|
Am. J. Hum. Genet. 65: 1368-1374, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10521302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10521302</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10521302[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=10521302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302616" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Ellis1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Roe, A. M., Kozloski, J., Proytcheva, M., Falk, C., German, J.
|
|
<strong>Linkage disequilibrium between the FES, D15S127, and BLM loci in Ashkenazi Jews with Bloom syndrome.</strong>
|
|
Am. J. Hum. Genet. 55: 453-460, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8079989/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8079989</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8079989" 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="13" class="mim-anchor"></a>
|
|
<a id="Foucault1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Foucault, F., Vaury, C., Barakat, A., Thibout, D., Planchon, P., Jaulin, C., Praz, F., Amor-Gueret, M.
|
|
<strong>Characterization of a new BLM mutation associated with a topoisomerase II-alpha defect in a patient with Bloom's syndrome.</strong>
|
|
Hum. Molec. Genet. 6: 1427-1434, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9285778/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9285778</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9285778" 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/6.9.1427" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Franchitto2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Franchitto, A., Pichierri, P.
|
|
<strong>Protecting genomic integrity during DNA replication: correlation between Werner's and Bloom's syndrome gene products and the MRE11 complex.</strong>
|
|
Hum. Molec. Genet. 11: 2447-2453, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12351580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12351580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12351580" 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/11.20.2447" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="German2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
German, J., Ellis, N.
|
|
<strong>Bloom syndrome. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. I. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001. P. 742.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="German2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
German, J., Sanz, M. M., Ciocci, S., Ye, T. Z., Ellis, N. A.
|
|
<strong>Syndrome-causing mutations of the BLM gene in persons in the Bloom's syndrome registry.</strong>
|
|
Hum. Mutat. 28: 743-753, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17407155/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17407155</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17407155" 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.20501" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Goss2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Goss, K. H., Risinger, M. A., Kordich, J. J., Sanz, M. M., Straughen, J. E., Slovek, L. E., Capobianco, A. J., German, J., Boivin, G. P., Groden, J.
|
|
<strong>Enhanced tumor formation in mice heterozygous for Blm mutation.</strong>
|
|
Science 297: 2051-2053, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242442/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242442</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12242442" 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.1074340" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Gruber2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gruber, S. B., Ellis, N. A., Scott, K. K., Almog, R., Kolachana, P., Bonner, J. D., Kirchhoff, T., Tomsho, L. P., Nafa, K., Pierce, H., Low, M., Satagopan, J., and 12 others.
|
|
<strong>BLM heterozygosity and the risk of colorectal cancer.</strong>
|
|
Science 297: 2013 only, 2002. Note: Erratum: Science 298: 751 only, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12242432/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12242432</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12242432" 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.1074399" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Guo2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guo, G., Wang, W., Bradley, A.
|
|
<strong>Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells.</strong>
|
|
Nature 429: 891-895, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15215866" 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/nature02653" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Hu2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hu, L., Kim, T. M., Son, M. Y., Kim, S.-A., Holland, C. L., Tateishi, S., Kim, D. H., Yew, P. R., Montagna, C., Dumitrache, L. C., Hasty, P.
|
|
<strong>Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes.</strong>
|
|
Nature 501: 569-572, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24013173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24013173</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24013173[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=24013173" 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/nature12500" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Imamura2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Imamura, O., Campbell, J. L.
|
|
<strong>The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 8193-8198, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12826610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12826610</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12826610[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=12826610" 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.1431624100" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Kaneko1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kaneko, H., Orii, K. O., Matsui, E., Shimozawa, N., Fukao, T., Matsumoto, T., Shimamoto, A., Furuichi, Y., Hayakawa, S., Kasahara, K., Kondo, N.
|
|
<strong>BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal.</strong>
|
|
Biochem. Biophys. Res. Commun. 240: 348-353, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9388480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9388480</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9388480" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.1997.7648" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Karow2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Karow, J. K., Constantinou, A., Li, J.-L., West, S. C., Hickson, I. D.
|
|
<strong>The Bloom's syndrome gene product promotes branch migration of Holliday junctions.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 6504-6508, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10823897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10823897</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10823897[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=10823897" 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.100448097" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Killen2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Killen, M. W., Stults, D. M., Adachi, N., Hanakahi, L., Pierce, A. J.
|
|
<strong>Loss of Bloom syndrome protein destabilizes human gene cluster architecture.</strong>
|
|
Hum. Molec. Genet. 18: 3417-3428, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19542097/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19542097</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19542097" 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/ddp282" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Kusano2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kusano, K., Johnson-Schlitz, D. M., Engels, W. R.
|
|
<strong>Sterility of Drosophila with mutations in the Bloom syndrome gene--complementation by Ku70.</strong>
|
|
Science 291: 2600-2602, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11283371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11283371</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11283371" 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.291.5513.2600" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Lillard-Wetherell2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lillard-Wetherell, K., Machwe, A., Langland, G. T., Combs, K. A., Behbehani, G. K., Schonberg, S. A., German, J., Turchi, J. J., Orren, D. K., Groden, J.
|
|
<strong>Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2.</strong>
|
|
Hum. Molec. Genet. 13: 1919-1932, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15229185/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15229185</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15229185" 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/ddh193" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Lindor2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lindor, N. M., Furuichi, Y., Kitao, S., Shimamoto, A., Arndt, C., Jalal, S.
|
|
<strong>Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome.</strong>
|
|
Am. J. Med. Genet. 90: 223-228, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10678659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10678659</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10678659" 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/(sici)1096-8628(20000131)90:3<223::aid-ajmg7>3.0.co;2-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Meetei2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E., Wang, W.
|
|
<strong>A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.</strong>
|
|
Molec. Cell. Biol. 23: 3417-3426, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12724401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12724401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12724401[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=12724401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1128/MCB.23.10.3417-3426.2003" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Mimitou2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mimitou, E. P., Symington, L. S.
|
|
<strong>Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.</strong>
|
|
Nature 455: 770-774, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18806779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18806779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18806779[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=18806779" 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/nature07312" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Mohaghegh2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mohaghegh, P., Hickson, I. D.
|
|
<strong>DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders.</strong>
|
|
Hum. Molec. Genet. 10: 741-746, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11257107/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11257107</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11257107" 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/10.7.741" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Oddoux1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Oddoux, C., Clayton, C. M., Nelson, H. R., Ostrer, H.
|
|
<strong>Prevalence of Bloom syndrome heterozygotes among Ashkenazi Jews. (Letter)</strong>
|
|
Am. J. Hum. Genet. 64: 1241-1243, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10090915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10090915</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10090915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/302312" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Opresko2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Opresko, P. L., von Kobbe, C., Laine, J.-P., Harrigan, J., Hickson, I. D., Bohr, V. A.
|
|
<strong>Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.</strong>
|
|
J. Biol. Chem. 277: 41110-41119, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12181313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12181313</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12181313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M205396200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Stavropoulos2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stavropoulos, D. J., Bradshaw, P. S., Li, X., Pasic, I., Truong, K., Ikura, M., Ungrin, M., Meyn, M. S.
|
|
<strong>The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.</strong>
|
|
Hum. Molec. Genet. 11: 3135-3144, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12444098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12444098</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12444098" 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/11.25.3135" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Straughen1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Straughen, J. E., Johnson, J., McLaren, D., Proytcheva, M., Ellis, N., German, J., Groden, J.
|
|
<strong>A rapid method for detecting the predominant Ashkenazi Jewish mutation in the Bloom's syndrome gene.</strong>
|
|
Hum. Mutat. 11: 175-178, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9482582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9482582</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9482582" 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/(SICI)1098-1004(1998)11:2<175::AID-HUMU11>3.0.CO;2-W" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="von Kobbe2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
von Kobbe, C., Karmakar, P., Dawut, L., Opresko, P., Zeng, X., Brosh, R. M., Jr., Hickson, I. D., Bohr, V. A.
|
|
<strong>Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.</strong>
|
|
J. Biol. Chem. 277: 22035-22044, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11919194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11919194</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11919194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M200914200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Walpita1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Walpita, D., Plug, A. W., Neff, N. F., German, J., Ashley, T.
|
|
<strong>Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 5622-5627, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10318934/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10318934</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10318934[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=10318934" 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.96.10.5622" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Wan2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wan, L., Han, J., Liu, T., Dong, S., Xie, F., Chen, H., Huang, J.
|
|
<strong>Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.</strong>
|
|
Proc. Nat. Acad. Sci. 110: 10646-10651, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23509288/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23509288</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23509288[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=23509288" 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.1220921110" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Wang2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., Qin, J.
|
|
<strong>BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.</strong>
|
|
Genes Dev. 14: 927-939, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10783165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10783165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10783165[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=10783165" 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="39" class="mim-anchor"></a>
|
|
<a id="Wechsler2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wechsler, T., Newman, S., West, S. C.
|
|
<strong>Aberrant chromosome morphology in human cells defective for Holliday junction resolution.</strong>
|
|
Nature 471: 642-646, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21399624/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21399624</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21399624[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=21399624" 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/nature09790" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Wu2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, L., Davies, S. L., North, P. S., Goulaouic, H., Riou, J.-F., Turley, H., Gatter, K. C., Hickson, I. D.
|
|
<strong>The Bloom's syndrome gene product interacts with topoisomerase III.</strong>
|
|
J. Biol. Chem. 275: 9636-9644, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10734115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10734115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10734115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.275.13.9636" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Wu2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wu, L., Hickson, I. D.
|
|
<strong>The Bloom's syndrome helicase suppresses crossing over during homologous recombination.</strong>
|
|
Nature 426: 870-874, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14685245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14685245</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14685245" 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/nature02253" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Yankiwski2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yankiwski, V., Marciniak, R. A., Guarente, L., Neff, N. F.
|
|
<strong>Nuclear structure in normal and Bloom syndrome cells.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 5214-5219, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10779560/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10779560</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10779560[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=10779560" 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.090525897" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Yusa2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yusa, K., Horie, K., Kondoh, G., Kouno, M., Maeda, Y., Kinoshita, T., Takeda, J.
|
|
<strong>Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.</strong>
|
|
Nature 429: 896-899, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15215867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15215867</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15215867" 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/nature02646" 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 : 10/28/2013
|
|
</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">
|
|
Patricia A. Hartz - updated : 8/27/2013<br>Paul J. Converse - updated : 5/3/2012<br>Ada Hamosh - updated : 6/29/2011<br>George E. Tiller - updated : 7/7/2010<br>Paul J. Converse - updated : 11/19/2008<br>George E. Tiller - updated : 5/30/2008<br>Cassandra L. Kniffin - updated : 10/10/2007<br>George E. Tiller - updated : 1/16/2007<br>Patricia A. Hartz - updated : 1/18/2005<br>Marla J. F. O'Neill - updated : 12/22/2004<br>George E. Tiller - updated : 9/2/2004<br>Ada Hamosh - updated : 7/22/2004<br>Ada Hamosh - updated : 12/30/2003<br>George E. Tiller - updated : 12/3/2003<br>Victor A. McKusick - updated : 8/27/2003<br>Patricia A. Hartz - updated : 7/7/2003<br>Ada Hamosh - updated : 2/6/2003<br>Patricia A. Hartz - updated : 1/7/2003<br>Patricia A. Hartz - updated : 12/16/2002<br>Ada Hamosh - updated : 9/30/2002<br>George E. Tiller - updated : 6/19/2001<br>Ada Hamosh - updated : 4/4/2001<br>Victor A. McKusick - updated : 3/13/2001<br>Paul J. Converse - updated : 11/16/2000<br>Ada Hamosh - updated : 8/31/2000<br>Victor A. McKusick - updated : 8/7/2000<br>Victor A. McKusick - updated : 7/26/2000<br>Victor A. McKusick - updated : 2/25/2000
|
|
</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">
|
|
Victor A. McKusick : 2/25/2000
|
|
</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 : 03/20/2024
|
|
</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 : 08/23/2022<br>carol : 08/22/2022<br>carol : 09/30/2016<br>carol : 07/09/2016<br>carol : 6/15/2016<br>alopez : 10/28/2013<br>mgross : 8/27/2013<br>terry : 3/14/2013<br>carol : 5/24/2012<br>carol : 5/24/2012<br>mgross : 5/9/2012<br>carol : 5/8/2012<br>mgross : 5/4/2012<br>terry : 5/3/2012<br>alopez : 7/6/2011<br>terry : 6/29/2011<br>wwang : 6/24/2011<br>terry : 9/9/2010<br>alopez : 7/21/2010<br>terry : 7/7/2010<br>mgross : 11/19/2008<br>terry : 11/19/2008<br>wwang : 6/5/2008<br>terry : 5/30/2008<br>ckniffin : 2/5/2008<br>wwang : 10/16/2007<br>ckniffin : 10/10/2007<br>wwang : 1/25/2007<br>terry : 1/16/2007<br>mgross : 4/14/2005<br>mgross : 1/18/2005<br>carol : 1/12/2005<br>carol : 1/12/2005<br>terry : 12/22/2004<br>carol : 9/3/2004<br>terry : 9/2/2004<br>alopez : 7/26/2004<br>terry : 7/22/2004<br>alopez : 7/6/2004<br>alopez : 12/31/2003<br>terry : 12/30/2003<br>mgross : 12/3/2003<br>tkritzer : 8/28/2003<br>tkritzer : 8/27/2003<br>carol : 8/8/2003<br>carol : 7/10/2003<br>mgross : 7/7/2003<br>alopez : 5/29/2003<br>alopez : 5/29/2003<br>terry : 5/29/2003<br>ckniffin : 3/11/2003<br>alopez : 2/10/2003<br>alopez : 2/10/2003<br>terry : 2/6/2003<br>mgross : 1/7/2003<br>mgross : 1/7/2003<br>mgross : 1/3/2003<br>terry : 12/16/2002<br>alopez : 9/30/2002<br>tkritzer : 9/30/2002<br>carol : 1/14/2002<br>cwells : 6/20/2001<br>cwells : 6/19/2001<br>alopez : 4/5/2001<br>terry : 4/4/2001<br>cwells : 3/27/2001<br>cwells : 3/26/2001<br>terry : 3/13/2001<br>joanna : 1/17/2001<br>joanna : 1/17/2001<br>joanna : 1/17/2001<br>joanna : 1/17/2001<br>mgross : 11/16/2000<br>alopez : 9/5/2000<br>terry : 8/31/2000<br>mcapotos : 8/28/2000<br>mcapotos : 8/10/2000<br>terry : 8/7/2000<br>mcapotos : 8/1/2000<br>mcapotos : 7/26/2000<br>mcapotos : 7/26/2000<br>alopez : 7/26/2000<br>terry : 7/20/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000
|
|
</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> 604610
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
RECQ PROTEIN-LIKE 3; RECQL3
|
|
|
|
</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">
|
|
DNA HELICASE, RECQ-LIKE, TYPE 2; RECQ2<br />
|
|
BLM GENE; BLM
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: BLM</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 4434006;
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 15q26.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 15:90,717,346-90,816,166 </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="1">
|
|
<span class="mim-font">
|
|
15q26.1
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Bloom syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
210900
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</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>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The RecQ gene family is named after the E. coli gene. RecQ is an E. coli gene that is a member of the RecF recombination pathway, a pathway of genes in which mutations abolish the conjugational recombination proficiency and ultraviolet resistance of a mutant strain. RECQL (600537) is a human gene isolated from HeLa cells, the product of which possesses DNA-dependent ATPase, DNA helicase, and 3-prime-to-5-prime single-stranded DNA translocation activities.</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>The hypermutability of Bloom syndrome (BLM; 210900) cells includes hyperrecombinability. Ellis et al. (1995) noted that although cells from all persons with Bloom syndrome exhibit the diagnostic high sister chromatid exchange (SCE) rate, in some persons a minor population of low SCE lymphocytes exist in the blood. Lymphoblastoid cell lines (LCLs) with low SCE rates can be developed from these low SCE lymphocytes. In multiple low SCE LCLs examined from 11 patients with BS, polymorphic loci distal to BLM on 15q had become homozygous in LCLs from 5 persons, whereas polymorphic loci proximal to the BLM locus remained heterozygous in all low SCE LCLs. These observations supported the hypothesis that low SCE lymphocytes arose through recombination within the BLM locus in persons with BS who had inherited paternally and maternally derived BLM alleles mutated at different sites. Such a recombination event in a precursor stem cell in these compound heterozygotes thus gave rise to a cell whose progeny had a functionally wildtype gene and phenotypically a low SCE rate (Ellis et al., 1995). Ellis et al. (1995) used the low SCE LCLs in which reduction to homozygosity had occurred for localizing BLM by an approach referred to as somatic crossover point (SCP) mapping. The precise map position of BLM was determined by comparing the genotypes of the recombinant low SCE LCLs from the 5 persons mentioned above with their constitutional genotypes at loci in the region around BLM. The strategy was to identify the most proximal polymorphic locus possible that was constitutionally heterozygous and that had been reduced to homozygosity in the low SCE LCLs, and to identify the most distal polymorphic locus possible that had remained constitutionally heterozygous in them. The BLM gene would have to be in the short interval defined by the reduced (distal) and the unreduced (proximal) heterozygous markers. The power of this approach was limited only by the density of polymorphic loci available in the immediate vicinity of BLM. A candidate for BLM was identified by direct selection of a cDNA derived from a 250-kb segment of the genome in 15q26.1 to which BLM had been assigned by SCP mapping. cDNA analysis of the candidate gene identified a 4,437-bp cDNA that encoded a 1,417-amino acid peptide with homology to the RecQ helicases, a subfamily of DExH box-containing DNA and RNA helicases. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The RECQL3 gene maps to chromosome 15q26.1 (Ellis et al., 1995). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Ellis and German (1996) reported that the BLM protein has similarity to 2 other proteins that are members of the RecQ family of helicases, namely the gene product encoded by RECQL2 (604611), also called WRN, and the product of the yeast gene Sgs1. Sgs1 was identified by a mutation that suppressed the slow-growth phenotype of mutations in the topoisomerase gene (see 126420). These proteins have 42 to 44% amino acid identity across the conserved helicase motifs. In addition, the proteins are of similar length and contain highly negatively charged N-terminal regions and highly positively charged C-terminal regions. Ellis and German (1996) noted that these similarities in overall structure have raised the possibility that the proteins play similar roles in metabolism. Since the Sgs1 gene product is known to interact with the products of the yeast topoisomerase genes, they predicted that the BLM and WRN genes interact with human topoisomerases. </p><p>Ellis et al. (1999) described the effects on the abnormal cellular phenotype of BS, namely an excessive rate of SCE, when normal BLM cDNA was stably transfected into 2 types of BS cells, SV40-transformed fibroblasts and Epstein-Barr virus-transformed lymphoblastoid cells. The experiments proved that BLM cDNA encodes a functional protein capable of restoring to or toward normal the uniquely characteristic high-SCE phenotype of BS cells. </p><p>In an immunocytologic study of mouse spermatocytes, Walpita et al. (1999) showed that the BLM protein is first evident as discrete foci along the synaptonemal complexes of homologously synapsed autosomal bivalents in late zygonema of meiotic prophase. BLM foci progressively dissociated from the synapsed autosomal axes during early pachynema and were no longer seen in mid-pachynema. BLM colocalized with the single-stranded DNA-binding replication protein A (see 179835), which had been shown to be involved in meiotic synapsis. However, there was a temporary delay in the appearance of BLM protein along the synaptonemal complexes relative to replication protein A, suggesting that BLM is required for a late step in processing of a subset of genomic DNA involved in establishment of interhomolog interactions in early meiotic prophase. In late pachynema and into diplonema, BLM is more dispersed in the nucleoplasm, especially over the chromatin most intimately associated with the synaptonemal complexes, suggesting a possible involvement of BLM in resolution of interlocks in preparation for homologous chromosome disjunction during anaphase I. </p><p>Yankiwski et al. (2000) found that the BLM protein is located in the nucleus of normal human cells in the nuclear domain 10 (ND10; see 604587) or promyelocytic leukemia nuclear bodies. These structures are punctate deposits of proteins disrupted upon viral infection and in certain human malignancies. BLM was found primarily in ND10 except during S phase, when it colocalized with the WRN gene product, in the nucleolus. BLM colocalized with a select subset of telomeres in normal cells and with large telomeric clusters seen in simian virus 40-transformed normal fibroblasts. During S phase, Bloom syndrome cells expel micronuclei containing sites of DNA synthesis. The BLM protein is likely to be part of a DNA surveillance mechanism operating during S phase. </p><p>Von Kobbe et al. (2002) confirmed interaction between BLM and WRN in immunoprecipitates of soluble nuclear extracts of HeLa cells. Immunolocalization of endogenous BLM and exogenously expressed WRN in several human cell lines showed colocalization of the 2 helicases in some nuclear foci and not in others, suggesting that their interaction is dynamic. Using pull-down assays with several truncation mutants, von Kobbe et al. (2002) determined that the BLM-binding regions of WRN include the N-terminal exonuclease domain and the RQC-containing regions. They mapped the WRN-binding region of BLM to the middle of the molecule. Von Kobbe et al. (2002) showed that BLM, by binding the exonuclease domain of WRN, inhibited WRN exonuclease activity. BLM had no effect on WRN helicase activity. </p><p>Bloom syndrome cells show marked genomic instability; in particular, hyperrecombination between sister chromatids and homologous chromosomes. Karow et al. (2000) investigated the mechanism by which the BLM protein normally suppresses hyperrecombination. They showed that in vitro BLM selectively binds Holliday junctions formed during genetic recombination and acts on recombination intermediates containing a Holliday junction to promote ATP-dependent branch migration. They presented a model in which BLM disrupts potentially recombinogenic molecules that arise at sites of stalled replication forks. They suggested that their results have implications for the role of BLM as an antirecombinase in the suppression of tumorigenesis. </p><p>Using various truncations of the BLM protein attached to green fluorescent protein, Kaneko et al. (1997) found that only the BLM protein truncated at amino acid 1357, containing an intact helicase domain and 2 arms, was transported to the nucleus, indicating that BLM protein translocates into the nucleus and that the distal arm of the bipartite basic residues in the C terminus of the BLM protein is essential for targeting the nucleus. </p><p>Wang et al. (2000) used immunoprecipitation and mass spectrometry analyses to identify BRCA1 (113705)-associated proteins. They found that BRCA1 is part of a large multisubunit protein complex of tumor suppressors, DNA damage sensors, and signal transducers. They named this complex BASC, for 'BRCA1-associated genome surveillance complex.' Among the DNA repair proteins identified in the complex were ATM (607585), BLM, MSH2 (609309), MSH6 (600678), MLH1 (120436), the RAD50 (604040)-MRE11 (600814)-NBS1 (602667) complex, and the RFC1 (102579)-RFC2 (600404)-RFC4 (102577) complex. Confocal microscopy demonstrated that BRCA1, BLM, and the RAD50-MRE11-NBS1 complex colocalize to large nuclear foci. Wang et al. (2000) suggested that BASC may serve as a sensor of abnormal DNA structures and/or as a regulator of the postreplication repair process. </p><p>By coimmunoprecipitation and in vitro pull-down assays, Beamish et al. (2002) verified direct interaction between ATM and BLM. By mutation analysis, they mapped the BLM-binding domain of ATM to residues 82 through 89. The ATM-binding region of BLM mapped to residues 636 to 1,074. Beamish et al. (2002) determined that the mitosis-associated hyperphosphorylation of BLM was partially dependent upon ATM phosphorylating thr99 and thr122 in the N-terminal region of BLM. Radiation-induced phosphorylation of BLM at thr99 was dose-dependent in normal cells and was defective in AT cells. BS lymphoblasts showed radiosensitivity that could be corrected by transfection of wildtype BLM but not by transfection of a thr99 phosphorylation-minus mutant. This phosphorylation-minus mutant did not alter SCE frequency, indicating that radiosensitivity and increased SCE are mediated by separate BLM domains. </p><p>Wu et al. (2000) determined that BLM and topoisomerase III-alpha (TOP3A; 601243) colocalized in the nucleus of human cells and coimmunoprecipitated from cell extracts. By in vitro binding assays with truncated BLM mutants, the authors identified 2 independent domains that mediate the interaction with TOP3A. One domain resides between residues 143 and 212 in the N-terminal domain of BLM, and the other resides between residues 1266 and 1417 in the C-terminal domain. </p><p>Dutertre et al. (2002) noted that BLM is phosphorylated and is excluded from the nuclear matrix during mitosis. BLM immunopurified from mitosis-arrested HeLa cells was phosphorylated and showed 3-prime-to-5-prime DNA helicase activity. Coimmunoprecipitation experiments revealed that phosphorylated BLM interacted with TOP3A. BLM was dephosphorylated in response to ionizing radiation and by inhibition of CDC2 (116940)/cyclin B (123836). Upon dephosphorylation, BLM relocalized to an insoluble subcellular compartment. </p><p>Mohaghegh and Hickson (2001) reviewed the DNA helicase deficiencies associated with cancer predisposition and premature aging disorders. </p><p>Opresko et al. (2002) found that, in vitro, TRF2 (602027) showed high affinity for BLM and for WRN, and that TRF2 interaction with either helicase resulted in stimulation of its activity. WRN or BLM, partnered with replication protein A (RPA; see 179835), actively unwound long telomeric duplex regions that were pre-bound by TRF2. </p><p>Telomerase-negative immortalized human cells maintain telomeres by alternative lengthening of telomeres (ALT) pathway(s), which may involve homologous recombination. Stavropoulos et al. (2002) found that endogenous BLM protein colocalized with telomeric foci in ALT human cells but not telomerase-positive immortal cell lines or primary cells. BLM interacted in vivo with the telomeric protein TRF2 in ALT cells, as detected by FRET and coimmunoprecipitation. Transient overexpression of GFP-BLM resulted in marked, ALT cell-specific increases in telomeric DNA. The association of BLM with telomeres and its effect on telomere DNA synthesis required a functional helicase domain. The authors suggested that BLM may facilitate recombination-driven amplification of telomeres in ALT cells. </p><p>Franchitto and Pichierri (2002) reviewed the roles of RECQL2 and RECQL3 in resolution of a stall in DNA replication, as well as their possible interaction with the MRE11-RAD50-NBS1 complex. Components of this complex are mutated in 2 genetic instability syndromes, Nijmegen breakage syndrome (251260) and ataxia telangiectasia-like disorder (604391). </p><p>Imamura and Campbell (2003) showed that the human BLM gene can suppress both the temperature-sensitive growth defect and the DNA damage sensitivity of the yeast DNA replication mutant Dna2-1. This yeast mutant is defective in a helicase/nuclease that is required either to coordinate with the crucial Fen1 nuclease of the yeast in Okazaki fragment maturation or to compensate for yeast Fen1 when its activity is impaired. Using coimmunoprecipitation from yeast extracts, Imamura and Campbell (2003) showed that human BLM interacts with both Dna2 and Fen1 of S. cerevisiae, suggesting that it participates in the same steps of DNA replication or repair as these 2 yeast proteins. </p><p>Wu and Hickson (2003) demonstrated that BLM and TOP3A together effect the resolution of a recombination intermediate containing a double Holliday junction. The mechanism, which they termed double-junction dissolution, is distinct from classical Holliday junction resolution and prevents exchange of flanking sequences. Loss of such an activity explains many of the cellular phenotypes of Bloom syndrome. Wu and Hickson (2003) proposed that double Holliday junctions are formed during the homologous recombination-dependent repair of daughter strand gaps that arise during replication, and that the dissolution of these double Holliday junctions by BLM prevents the diagnostically high sister chromatid exchange frequency seen in Bloom syndrome cells. Furthermore, BLM-catalyzed double-junction dissolution may act to suppress tumorigenesis by preventing loss of heterozygosity, a feature associated with BLM deficiency in mice, through the suppression of ectopic recombination and crossing-over between homologous chromosomes. </p><p>By coimmunoprecipitation of HeLa cell nuclear extracts, Meetei et al. (2003) identified 3 distinct multiprotein complexes associated with BLM, all of which were different from the BASC complex reported by Wang et al. (2000). One of the complexes, designated BRAFT, contained the Fanconi anemia core complementation group proteins FANCA (607139), FANCG (602956), FANCC (613899), FANCE (613976), and FANCF (613897), as well as Topo III-alpha and RPA. BLM complexes isolated from an FA cell line had a lower molecular mass, likely due to loss of FANCA and other FA components. BLM- and FANCA-associated complexes had DNA unwinding activity, and BLM was required for this activity. </p><p>Lillard-Wetherell et al. (2004) reported that BLM colocalized and complexed with TERF2 (602027) in cells that employ ALT. BLM colocalized with TERF2 in foci actively synthesizing DNA during late S and G2/M; colocalization increased in late S and G2/M when ALT is thought to occur. TERF1 (600951) and TERF2 interacted directly with BLM and regulated its unwinding activity in vitro. Whereas TERF2 stimulated BLM unwinding of telomeric and nontelomeric substrates, TERF1 inhibited its unwinding of telomeric substrates only. TERF2 stimulated BLM unwinding with equimolar concentrations of TERF1 but not when TRF1 was added in molar excess. Lillard-Wetherell et al. (2004) proposed a function for BLM in recombination-mediated telomere lengthening and a model for the coordinated regulation of BLM activity at telomeres by TERF1 and TERF2. </p><p>Eladad et al. (2005) showed that BLM is a substrate for SUMO1 (601912) modification, with lys317, lys331, lys334, and lys347 being preferred sites of modification. Unlike normal BLM, a double-mutant BLM protein with lysine-to-arginine substitutions at residues 317 and 331 was not modified by SUMO1, and it failed to localize efficiently to the PML nuclear bodies. Rather, double-mutant BLM protein induced the formation of DNA damage-induced foci (DDI) that contained BRCA1 (113705) protein and phosphorylated histone H2AX (601772). Double-mutant BLM only partially complemented the genomic instability phenotypes of Bloom syndrome cells as assessed by sister-chromatid exchange and micronuclei formation assays. Eladad et al. (2005) hypothesized that BLM is a DNA damage sensor that signals the formation of DDI, for which SUMO1 modification is a negative regulator of BLM signaling function. </p><p>Mimitou and Symington (2008) demonstrated that yeast Exo1 nuclease (606063) and Sgs1 helicase functioned in alternative pathways for double-strand break (DSB) processing. Novel, partially resected intermediates, whose initial generation depended on Sae2 (see 604124), accumulated in yeast lacking both Exo1 and Sgs1 and were poor substrates for homologous recombination. When Sae2 was absent, in addition to Exo1 and Sgs1, homology-dependent repair failed and unprocessed DSBs accumulated. Mimitou and Symington (2008) concluded that there is a 2-step mechanism for DSB processing during homologous recombination, with the Mre11 complex and Sae2 removing a small oligonucleotide from DNA ends to form an early intermediate, followed by processing of this intermediate by Exo1 and/or Sgs1 to generate extensive tracts of single-stranded DNA that serve as a substrate for Rad51 (179617). Since BLM is the human homolog of Sgs1, the results suggested that some of the defects observed in Bloom syndrome could be due to altered DSB processing. </p><p>Killen et al. (2009) used physical analysis of the highly repeated, self-similar ribosomal RNA gene clusters as sentinel biomarkers for dysregulated homologous recombination to demonstrate that loss of BLM protein function caused a striking increase in spontaneous molecular-level genomic restructuring. Analysis of single cell-derived subclonal populations from wildtype human cell lines showed that gene cluster architecture is ordinarily faithfully preserved under mitosis, but was so unstable in cell lines derived from BLMs as to make gene cluster architecture in different subclonal populations unrecognizable one from another. Cells defective in a different RecQ helicase, the WRN (RECQL2; 604611) protein, did not exhibit the gene cluster instability (GCI) phenotype, indicating that the BLM protein specifically, rather than RecQ helicases generally, held back this recombination-mediated genomic instability. An ATM (607585)-defective cell line also showed elevated rDNA GCI, although not to the extent of BLM-defective cells. Killen et al. (2009) hypothesized that genomic restructuring mediated by dysregulated recombination between the abundant low-copy repeats in the human genome may be an important additional mechanism of genomic instability driving the initiation and progression of human cancer. </p><p>Wechsler et al. (2011) used Bloom syndrome cells, in which the BLM gene is inactive, to analyze human cells compromised for the known Holliday junction dissolution/resolution pathways. Wechsler et al. (2011) showed that depletion of MUS81 (606591) and GEN1 (612449), or SLX4 (613278) and GEN1, from Bloom syndrome cells results in severe chromosome abnormalities, such that sister chromatids remain interlinked in a side-by-side arrangement and the chromosomes are elongated and segmented. Wechsler et al. (2011) concluded that normally replicating human cells require Holliday junction processing activities to prevent sister chromatid entanglements and thereby ensure accurate chromosome condensation. This phenotype was not apparent when both MUS81 and SLX4 were depleted from Bloom syndrome cells, suggesting that GEN1 can compensate for their absence. Additionally, Wechsler et al. (2011) showed that depletion of MUS81 or SLX4 reduces the high frequency of sister chromatid exchanges in Bloom syndrome cells, indicating that MUS81 and SLX4 promote sister chromatid exchange formation, in events that may ultimately drive the chromosome instabilities that underpin early-onset cancers associated with Bloom syndrome. </p><p>Using protein interaction assays with human cell lines and expression constructs, Wan et al. (2013) showed that BLM interacted with endogenous SPIDR (615384), a nuclear scaffolding protein. Both proteins colocalized to nuclear foci following DNA damage in HeLa cells. Knockdown of SPIDR or BLM via small interfering RNA resulted in increased frequency of sister chromatid exchange following DNA damage and impaired RAD51 focus formation. Coimmunoprecipitation experiments showed that BLM interacted in a ternary complex with SPIDR and RAD51. Knockdown of SPIDR in HeLa cells reduced the association of BLM with RAD51 and increased the number of chromosomal aberrations and cell sensitivity to DNA damage. Wan et al. (2013) concluded that SPIDR provides a link between BLM and the homologous recombination machinery. </p><p>Hu et al. (2013) delineated 2 pathways that spontaneously fuse inverted repeats to generate unstable chromosomal rearrangements in wildtype mouse embryonic stem cells. Gamma radiation induced a RECQL3-regulated pathway that selectively fused identical, but not mismatched, repeats. By contrast, ultraviolet light induced a RAD18 (605256)-dependent pathway that efficiently fused mismatched repeats. In addition, TREX2 (300370), a 3-prime-to-5-prime exonuclease, suppressed identical repeat fusion but enhanced mismatched repeat fusion, clearly separating these pathways. TREX2 associated with UBC13 (603679) and enhanced PCNA (176740) ubiquitination in response to ultraviolet light, consistent with its being a novel member of error-free postreplication repair. RAD18 and TREX2 also suppressed replication fork stalling in response to nucleotide depletion. Replication fork stalling induced fusion for identical and mismatched repeats, implicating faulty replication as a causal mechanism for both pathways. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In patients with Bloom syndrome, Ellis et al. (1995) identified chain-terminating mutations in the BLM gene. Mutation analysis in the first 13 unrelated persons with BS examined permitted the identification of 7 unique mutations in 10 of them. The fact that 4 of the 7 mutations resulted in premature termination of translation indicated that the cause of most Bloom syndrome is the loss of enzymatic activity of the BLM gene product. Identification of loss-of-function mutations in BLM is consistent with the autosomal recessive transmission, and the homology of BLM and RecQ suggested that BLM has enzymatic activity. Ellis et al. (1995) suggested that the absence of the BLM gene product probably destabilizes other enzymes that participate in DNA replication and repair, perhaps through direct interaction and through more general responses to DNA damage. In 4 persons of Jewish ancestry, they detected a homozygous deletion/insertion mutation (604610.0001) in the BLM gene. Homozygosity was predictable because linkage disequilibrium had been detected in Ashkenazi Jews with Bloom syndrome between BLM, D15S127, and FES (Ellis et al., 1994). Thus a person who carried this deletion/insertion mutation was a founder of Ashkenazi Jewish population and nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. </p><p>In a patient with Bloom syndrome and both high- and low-SCE cell lines, Foucault et al. (1997) identified compound heterozygosity for a cys1036-to-phe (C1036F; 604610.0004) substitution in the C-terminal region of the peptide and an unidentified mutation affecting expression of the RECQL3 gene. Foucault et al. (1997) concluded that somatic intragenic recombination resulted in cells that had an untranscribed allele carrying the 2 parental RECQL3 mutations and a wildtype allele which allowed reversion to the low SCE phenotype. Topoisomerase II-alpha (126430) mRNA and protein levels were decreased in the high SCE cells, whereas they were normal in the corresponding low SCE cells. Foucault et al. (1997) proposed that in addition to its putative helicase activity, RECQL3 might be involved in transcription regulation. </p><p>German et al. (2007) identified 64 different mutations in 125 of 134 individuals with Bloom syndrome from a patient registry. There were 54 mutations resulting in premature termination and 10 missense mutations. Several recurrent and founder mutations were identified. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Family</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In their Table I, Lindor et al. (2000) provided a comparison of the 5 human RECQ helicases identified to that time. The RECQL3 gene is deficient in Bloom syndrome. The RECQL2 gene is deficient in Werner syndrome (277700), and the RECQL4 gene (603780) is deficient in Rothmund-Thomson syndrome (268400). No disorder had been related to RECQ1 (RECQL) or RECQL5 (603781). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Chester et al. (1998) found that mouse embryos homozygous for a targeted mutation in the murine Bloom syndrome gene are developmentally delayed and die by embryonic day 13.5. They determined that the interrupted gene is the homolog of the human BLM gene by its homologous sequence, its chromosomal location, and the demonstration of high numbers of sister chromatid exchanges in cultured murine Blm -/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12 to 24 hours) seen during midgestation in murine Blm -/- embryos. The growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early postimplantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm -/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes. </p><p>Kusano et al. (2001) demonstrated that Drosophila Dmblm is identical to mus309, a locus originally identified in a mutagen-sensitivity screen. One mus309 allele, which carries a stop codon between 2 of the helicase motifs, causes partial male sterility and complete female sterility. Mutant males produce an excess of XY sperm and nullo sperm, consistent with a high frequency of nondisjunction and/or chromosome loss. These phenotypes of mus309 suggest that Dmblm functions in DNA double-strand break repair. The mutant Dmblm phenotypes were partially rescued by an extra copy of the DNA repair gene Ku70 (152690), indicating that the 2 genes functionally interact in vivo. </p><p>Goss et al. (2002) used homologous recombination to disrupt the mouse Blm gene to simulate BLM(Ash), a frameshift mutation in the BLM gene present in 1% of Ashkenazi Jews. Mice heterozygous for this mutation developed lymphoma earlier than wildtype littermates in response to challenge with murine leukemia virus at birth and twice the number of intestinal tumors when crossed with mice carrying mutation in the APC gene (611731). Goss et al. (2002) concluded that Blm is a modifier of tumor formation in the mouse and that Blm haploinsufficiency is associated with tumor predisposition. </p><p>Adams et al. (2003) studied the Drosophila BLM ortholog MUS309 and demonstrated that mutants are severely impaired in their ability to carry out repair DNA synthesis during synthesis-dependent strand annealing. Consequently, repair in the mutants is completed by error-prone pathways that create large deletions. Adams et al. (2003) concluded that their results suggested a model in which BLM maintains genomic stability by promoting efficient repair DNA synthesis and thereby prevents double-strand break repair by less precise pathways. </p><p>Guo et al. (2004) exploited the high rate of mitotic recombination in Bloom syndrome protein (Blm)-deficient embryonic stem cells to generate a genomewide library of homozygous mutant cells from heterozygous mutations induced with a revertible gene trap retrovirus. Guo et al. (2004) screened this library for cells with defects in DNA mismatch repair (MMR), a system that detects and repairs base-base mismatches. They demonstrated the recovery of cells with homozygous mutations in known and novel mismatch repair genes. Guo et al. (2004) identified DNMT1 (126375) as a novel MMR gene and confirmed that Dnmt1-deficient embryonic stem cells exhibit microsatellite instability, providing a mechanistic explanation for the role of DNMT1 in cancer. </p><p>Yusa et al. (2004) used a tetracycline-regulated Blm allele, Blm(tet), to introduce biallelic mutations across the genome in mouse embryonic stem cells. Transient loss of Blm expression induced homologous recombination not only between sister chromatids but also between homologous chromosomes. Yusa et al. (2004) considered that the phenotype of embryonic stem cells bearing biallelic mutations would be maintained after withdrawal of the tetracycline analog doxycycline. Indeed, a combination of N-ethyl-N-nitrosourea mutagenesis and transient loss of Blm expression enabled them to generate an embryonic stem cell library with genomewide biallelic mutations. The library was evaluated by screening for mutants of glycosylphosphatidylinositol-anchor biosynthesis, which involves at least 23 genes distributed throughout the genome. Mutants derived from 12 different genes were obtained and 2 unknown mutants were simultaneously isolated. Yusa et al. (2004) concluded that their results indicated that phenotype-based genetic screening with Blm(tet) is very efficient and raises possibilities for identifying gene functions in embryonic stem cells. </p><p>Babbe et al. (2009) found that specific inactivation of Blm in mouse B cells in vivo drastically reduced both developing B cells in bone marrow and mature B cells in the periphery, particularly the B1a subset. Serum concentrations of all Ig subtypes were low, even after immunization. Blm -/- B cells had reduced antibody class switch capacity in vitro, but Blm was not critical for class switch recombination. Mice with Blm -/- B cells that also lacked p53 (TP53; 191170) had increased propensity to develop B-cell lymphoma due to high rates of chromosomal structural abnormalities and impaired cell cycle progression. Babbe et al. (2009) concluded that BLM ensures proper development and function of the various B-cell subsets and also counteracts lymphomagenesis. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>4 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BLM, 6-BP DEL/7-BP INS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs113993962,
|
|
|
|
|
|
gnomAD: rs113993962,
|
|
|
|
|
|
ClinVar: RCV000005787, RCV000058933, RCV000562115, RCV004745147
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 4 ostensibly unrelated persons of Jewish ancestry with Bloom syndrome (BLM; 210900), Ellis et al. (1995) found homozygosity for a 6-bp deletion/7-bp insertion at nucleotide 2281 of the BLM cDNA. Deletion of ATCTGA and insertion of TAGATTC caused the insertion of the novel codons for LDSR after amino acid 736, and after these codons there was a stop codon. Ellis et al. (1995) concluded that a person carrying this deletion/insertion mutation was a founder of the Ashkenazi-Jewish population, and that nearly all Ashkenazi Jews with Bloom syndrome inherited the mutation identical by descent from this common ancestor. Identification of the mutation by a PCR test was now possible for screening for carriers among Ashkenazim. </p><p>Straughen et al. (1998) described a rapid method for detecting the 6-bp deletion/7-bp insertion, a predominant Ashkenazi Jewish mutation in Bloom syndrome. They commented that in the Bloom syndrome registry, one or both parents of 52 of the 168 registered persons are Ashkenazi Jews. </p><p>Using a convenient PCR assay, Ellis et al. (1998) found the 6-bp del/7-bp ins mutation, blm(Ash), on 58 of 60 chromosomes transmitted by Ashkenazi parents to persons with Bloom syndrome. In contrast, in 91 unrelated non-Ashkenazic persons with BS whom they examined, blm(Ash) was identified in only 5, these coming from Spanish-speaking Christian families from the southwestern United States, Mexico, or El Salvador. These data, along with haplotype analyses, showed that blm(Ash) was independently established through a founder effect in Ashkenazi Jews and in immigrants to formerly Spanish colonies. This striking observation underscored the complexity of Jewish history and demonstrated the importance of migration and genetic drift in the formation of human populations. </p><p>In a study of the frequency of the BLM 6-bp del/7-bp ins mutation in a group of Ashkenazi Jews, unselected for personal or family history of Bloom syndrome, Oddoux et al. (1999) found the mutation in 5 of 1,155 individuals, yielding a frequency of 1/231 (95% CI, 1/123-1/1,848). The low frequency is consistent with an absence of heterozygote advantage for carriers of 1 copy of the mutant allele. The frequency of heterozygotes for other autosomal recessive conditions within their panel had been validated in other studies, suggesting that the test panel was representative of the Ashkenazi Jewish population. Those frequencies were Tay-Sachs disease, 1/28; cystic fibrosis, 1/25; Gaucher disease, 1/15; BRCA2, 6174delT, 1/106; Canavan disease, 1/41; and Fanconi anemia complementation group C, 1/116. </p><p>To determine whether carriers of BLM mutations are at increased risk of colorectal cancer, Gruber et al. (2002) genotyped 1,244 cases of colorectal cancer and 1,839 controls, both of Ashkenazi Jewish ancestry, to estimate the relative risk of colorectal cancer among carriers of the BLM(Ash) founder mutation. Ashkenazi Jews with colorectal cancer were more than twice as likely to carry the BLM(Ash) mutation than Ashkenazi Jewish controls without colorectal cancer (odds ratio = 2.45, 95% CI 1.3 to 4.8; P = 0.0065). Gruber et al. (2002) verified that the APC I1307K mutation (611731.0029) did not confound their results. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BLM, 3-BP DEL, 631CAA
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs367543035,
|
|
|
|
|
|
|
|
ClinVar: RCV000005788
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with Bloom syndrome (BLM; 210900), Ellis et al. (1995) found homozygosity for a deletion of CAA at nucleotide position 631-633 in the BLM gene, resulting in a stop codon at amino acid position 186. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BLM, EX11,12DEL
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000034895
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Italian patient (BSR92) with Bloom syndrome (BLM; 210900), German et al. (2007) identified homozygosity for a large deletion in exons 11 and 12 in the RECQL3 gene (2308-953_2555+4719del6126), causing a frameshift (Ile770fs). (German and Ellis (2001) noted that the mutation in patient BSR92 was assigned incorrectly by Ellis et al. (1995). Ellis et al. (1995) had reported the patient to be homozygous for a 2596T-C transition resulting in an ile841-to-thr substitution. Table 1 in their article had erroneously stated that the change occurred at position 843.) </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 BLOOM SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
BLM, CYS1036PHE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853153,
|
|
|
|
|
|
|
|
ClinVar: RCV000005790
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with Bloom syndrome (BLM; 210900), Foucault et al. (1997) identified compound heterozygosity for a 3181G-T transversion in the RECQL3 gene, resulting in a cys1036-to-phe (C1036F) substitution in the C-terminal region of the peptide, and an unidentified mutation affecting expression of the RECQL3 gene. The patient was initially believed to be homozygous for the C1036F mutation, but SSCP analysis, direct sequencing of RT-PCR products, and EcoRI digestion using a restriction site created by the mutation showed that the mutation was not present in low SCE cells from the patient. No EcoRI digestion was observed on paternal PCR products. Partial EcoRI digestion was seen with PCR products from maternal and patient DNA and from high- and low-SCE cells from the patient, and direct sequencing confirmed the presence of both a wildtype and mutated sequence at nucleotide 3181 in the high- and low-SCE cell lines, indicating heterozygosity for the mutation. Foucault et al. (1997) concluded that somatic intragenic recombination resulted in cells that had an untranscribed allele carrying the 2 parental RECQL3 mutations and a wildtype allele which allowed reversion to the low-SCE phenotype. </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">
|
|
Adams, M. D., McVey, M., Sekelsky, J. J.
|
|
<strong>Drosophila BLM in double-strand break repair by synthesis-dependent strand annealing.</strong>
|
|
Science 299: 265-267, 2003.
|
|
|
|
|
|
[PubMed: 12522255]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1077198]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Babbe, H., McMenamin, J., Hobeika, E., Wang, J., Rodig, S. J., Reth, M., Leder, P.
|
|
<strong>Genomic instability resulting from Blm deficiency compromises development, maintenance, and function of the B cell lineage.</strong>
|
|
J. Immun. 182: 347-360, 2009.
|
|
|
|
|
|
[PubMed: 19109166]
|
|
|
|
|
|
[Full Text: https://doi.org/10.4049/jimmunol.182.1.347]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beamish, H., Kedar, P., Kaneko, H., Chen, P., Fukao, T., Peng, C., Beresten, S., Gueven, N., Purdie, D., Lees-Miller, S., Ellis, N., Kondo, N., Lavin, M. F.
|
|
<strong>Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM.</strong>
|
|
J. Biol. Chem. 277: 30515-30523, 2002.
|
|
|
|
|
|
[PubMed: 12034743]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M203801200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chester, N., Kuo, F., Kozak, C., O'Hara, C. D., Leder, P.
|
|
<strong>Stage-specific apoptosis, developmental delay, and embryonic lethality in mice homozygous for a targeted disruption in the murine Bloom's syndrome gene.</strong>
|
|
Genes Dev. 12: 3382-3393, 1998.
|
|
|
|
|
|
[PubMed: 9808625]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.12.21.3382]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dutertre, S., Sekhri, R., Tintignac, L. A., Onclercq-Delic, R., Chatton, B., Jaulin, C., Amor-Gueret, M.
|
|
<strong>Dephosphorylation and subcellular compartment change of the mitotic Bloom's syndrome DNA helicase in response to ionizing radiation.</strong>
|
|
J. Biol. Chem. 277: 6280-6286, 2002.
|
|
|
|
|
|
[PubMed: 11741924]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M105735200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eladad, S., Ye, T.-Z., Hu, P., Leversha, M., Beresten, S., Matunis, M. J., Ellis, N. A.
|
|
<strong>Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification.</strong>
|
|
Hum. Molec. Genet. 14: 1351-1365, 2005.
|
|
|
|
|
|
[PubMed: 15829507]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi145]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Ciocci, S., Proytcheva, M., Lennon, D., Groden, J., German, J.
|
|
<strong>The Ashkenazic Jewish Bloom syndrome mutation blm(Ash) is present in non-Jewish Americans of Spanish ancestry.</strong>
|
|
Am. J. Hum. Genet. 63: 1685-1693, 1998.
|
|
|
|
|
|
[PubMed: 9837821]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302167]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., German, J.
|
|
<strong>Molecular genetics of Bloom's syndrome.</strong>
|
|
Hum. Molec. Genet. 5: 1457-1463, 1996.
|
|
|
|
|
|
[PubMed: 8875252]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/5.supplement_1.1457]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Groden, J., Ye, T.-Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., German, J.
|
|
<strong>The Bloom's syndrome gene product is homologous to RecQ helicases.</strong>
|
|
Cell 83: 655-666, 1995.
|
|
|
|
|
|
[PubMed: 7585968]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(95)90105-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Lennon, D. J., Proytcheva, M., Alhadeff, B., Henderson, E. E., German, J.
|
|
<strong>Somatic intragenic recombination within the mutated locus BLM can correct the high SCE phenotype of Bloom syndrome cells.</strong>
|
|
Am. J. Hum. Genet. 57: 1019-1027, 1995. Note: Erratum: Am. J. Hum. Genet. 58: 254 only, 1996.
|
|
|
|
|
|
[PubMed: 7485150]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Proytcheva, M., Sanz, M. M., Ye, T.-Z., German, J.
|
|
<strong>Transfection of BLM into cultured Bloom syndrome cells reduces the sister-chromatid exchange rate toward normal.</strong>
|
|
Am. J. Hum. Genet. 65: 1368-1374, 1999.
|
|
|
|
|
|
[PubMed: 10521302]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302616]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellis, N. A., Roe, A. M., Kozloski, J., Proytcheva, M., Falk, C., German, J.
|
|
<strong>Linkage disequilibrium between the FES, D15S127, and BLM loci in Ashkenazi Jews with Bloom syndrome.</strong>
|
|
Am. J. Hum. Genet. 55: 453-460, 1994.
|
|
|
|
|
|
[PubMed: 8079989]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Foucault, F., Vaury, C., Barakat, A., Thibout, D., Planchon, P., Jaulin, C., Praz, F., Amor-Gueret, M.
|
|
<strong>Characterization of a new BLM mutation associated with a topoisomerase II-alpha defect in a patient with Bloom's syndrome.</strong>
|
|
Hum. Molec. Genet. 6: 1427-1434, 1997.
|
|
|
|
|
|
[PubMed: 9285778]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.9.1427]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Franchitto, A., Pichierri, P.
|
|
<strong>Protecting genomic integrity during DNA replication: correlation between Werner's and Bloom's syndrome gene products and the MRE11 complex.</strong>
|
|
Hum. Molec. Genet. 11: 2447-2453, 2002.
|
|
|
|
|
|
[PubMed: 12351580]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.20.2447]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
German, J., Ellis, N.
|
|
<strong>Bloom syndrome. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. I. (8th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 2001. P. 742.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
German, J., Sanz, M. M., Ciocci, S., Ye, T. Z., Ellis, N. A.
|
|
<strong>Syndrome-causing mutations of the BLM gene in persons in the Bloom's syndrome registry.</strong>
|
|
Hum. Mutat. 28: 743-753, 2007.
|
|
|
|
|
|
[PubMed: 17407155]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20501]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goss, K. H., Risinger, M. A., Kordich, J. J., Sanz, M. M., Straughen, J. E., Slovek, L. E., Capobianco, A. J., German, J., Boivin, G. P., Groden, J.
|
|
<strong>Enhanced tumor formation in mice heterozygous for Blm mutation.</strong>
|
|
Science 297: 2051-2053, 2002.
|
|
|
|
|
|
[PubMed: 12242442]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1074340]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gruber, S. B., Ellis, N. A., Scott, K. K., Almog, R., Kolachana, P., Bonner, J. D., Kirchhoff, T., Tomsho, L. P., Nafa, K., Pierce, H., Low, M., Satagopan, J., and 12 others.
|
|
<strong>BLM heterozygosity and the risk of colorectal cancer.</strong>
|
|
Science 297: 2013 only, 2002. Note: Erratum: Science 298: 751 only, 2002.
|
|
|
|
|
|
[PubMed: 12242432]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1074399]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guo, G., Wang, W., Bradley, A.
|
|
<strong>Mismatch repair genes identified using genetic screens in Blm-deficient embryonic stem cells.</strong>
|
|
Nature 429: 891-895, 2004.
|
|
|
|
|
|
[PubMed: 15215866]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature02653]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hu, L., Kim, T. M., Son, M. Y., Kim, S.-A., Holland, C. L., Tateishi, S., Kim, D. H., Yew, P. R., Montagna, C., Dumitrache, L. C., Hasty, P.
|
|
<strong>Two replication fork maintenance pathways fuse inverted repeats to rearrange chromosomes.</strong>
|
|
Nature 501: 569-572, 2013.
|
|
|
|
|
|
[PubMed: 24013173]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature12500]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Imamura, O., Campbell, J. L.
|
|
<strong>The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants.</strong>
|
|
Proc. Nat. Acad. Sci. 100: 8193-8198, 2003.
|
|
|
|
|
|
[PubMed: 12826610]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1431624100]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kaneko, H., Orii, K. O., Matsui, E., Shimozawa, N., Fukao, T., Matsumoto, T., Shimamoto, A., Furuichi, Y., Hayakawa, S., Kasahara, K., Kondo, N.
|
|
<strong>BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal.</strong>
|
|
Biochem. Biophys. Res. Commun. 240: 348-353, 1997.
|
|
|
|
|
|
[PubMed: 9388480]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.1997.7648]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karow, J. K., Constantinou, A., Li, J.-L., West, S. C., Hickson, I. D.
|
|
<strong>The Bloom's syndrome gene product promotes branch migration of Holliday junctions.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 6504-6508, 2000.
|
|
|
|
|
|
[PubMed: 10823897]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.100448097]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Killen, M. W., Stults, D. M., Adachi, N., Hanakahi, L., Pierce, A. J.
|
|
<strong>Loss of Bloom syndrome protein destabilizes human gene cluster architecture.</strong>
|
|
Hum. Molec. Genet. 18: 3417-3428, 2009.
|
|
|
|
|
|
[PubMed: 19542097]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp282]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kusano, K., Johnson-Schlitz, D. M., Engels, W. R.
|
|
<strong>Sterility of Drosophila with mutations in the Bloom syndrome gene--complementation by Ku70.</strong>
|
|
Science 291: 2600-2602, 2001.
|
|
|
|
|
|
[PubMed: 11283371]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.291.5513.2600]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lillard-Wetherell, K., Machwe, A., Langland, G. T., Combs, K. A., Behbehani, G. K., Schonberg, S. A., German, J., Turchi, J. J., Orren, D. K., Groden, J.
|
|
<strong>Association and regulation of the BLM helicase by the telomere proteins TRF1 and TRF2.</strong>
|
|
Hum. Molec. Genet. 13: 1919-1932, 2004.
|
|
|
|
|
|
[PubMed: 15229185]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddh193]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lindor, N. M., Furuichi, Y., Kitao, S., Shimamoto, A., Arndt, C., Jalal, S.
|
|
<strong>Rothmund-Thomson syndrome due to RECQ4 helicase mutations: report and clinical and molecular comparisons with Bloom syndrome and Werner syndrome.</strong>
|
|
Am. J. Med. Genet. 90: 223-228, 2000.
|
|
|
|
|
|
[PubMed: 10678659]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1096-8628(20000131)90:3<223::aid-ajmg7>3.0.co;2-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Meetei, A. R., Sechi, S., Wallisch, M., Yang, D., Young, M. K., Joenje, H., Hoatlin, M. E., Wang, W.
|
|
<strong>A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome.</strong>
|
|
Molec. Cell. Biol. 23: 3417-3426, 2003.
|
|
|
|
|
|
[PubMed: 12724401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/MCB.23.10.3417-3426.2003]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mimitou, E. P., Symington, L. S.
|
|
<strong>Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing.</strong>
|
|
Nature 455: 770-774, 2008.
|
|
|
|
|
|
[PubMed: 18806779]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature07312]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mohaghegh, P., Hickson, I. D.
|
|
<strong>DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders.</strong>
|
|
Hum. Molec. Genet. 10: 741-746, 2001.
|
|
|
|
|
|
[PubMed: 11257107]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/10.7.741]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Oddoux, C., Clayton, C. M., Nelson, H. R., Ostrer, H.
|
|
<strong>Prevalence of Bloom syndrome heterozygotes among Ashkenazi Jews. (Letter)</strong>
|
|
Am. J. Hum. Genet. 64: 1241-1243, 1999.
|
|
|
|
|
|
[PubMed: 10090915]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/302312]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Opresko, P. L., von Kobbe, C., Laine, J.-P., Harrigan, J., Hickson, I. D., Bohr, V. A.
|
|
<strong>Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases.</strong>
|
|
J. Biol. Chem. 277: 41110-41119, 2002.
|
|
|
|
|
|
[PubMed: 12181313]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M205396200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stavropoulos, D. J., Bradshaw, P. S., Li, X., Pasic, I., Truong, K., Ikura, M., Ungrin, M., Meyn, M. S.
|
|
<strong>The Bloom syndrome helicase BLM interacts with TRF2 in ALT cells and promotes telomeric DNA synthesis.</strong>
|
|
Hum. Molec. Genet. 11: 3135-3144, 2002.
|
|
|
|
|
|
[PubMed: 12444098]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/11.25.3135]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Straughen, J. E., Johnson, J., McLaren, D., Proytcheva, M., Ellis, N., German, J., Groden, J.
|
|
<strong>A rapid method for detecting the predominant Ashkenazi Jewish mutation in the Bloom's syndrome gene.</strong>
|
|
Hum. Mutat. 11: 175-178, 1998.
|
|
|
|
|
|
[PubMed: 9482582]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1998)11:2<175::AID-HUMU11>3.0.CO;2-W]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
von Kobbe, C., Karmakar, P., Dawut, L., Opresko, P., Zeng, X., Brosh, R. M., Jr., Hickson, I. D., Bohr, V. A.
|
|
<strong>Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins.</strong>
|
|
J. Biol. Chem. 277: 22035-22044, 2002.
|
|
|
|
|
|
[PubMed: 11919194]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M200914200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Walpita, D., Plug, A. W., Neff, N. F., German, J., Ashley, T.
|
|
<strong>Bloom's syndrome protein, BLM, colocalizes with replication protein A in meiotic prophase nuclei of mammalian spermatocytes.</strong>
|
|
Proc. Nat. Acad. Sci. 96: 5622-5627, 1999.
|
|
|
|
|
|
[PubMed: 10318934]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.96.10.5622]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wan, L., Han, J., Liu, T., Dong, S., Xie, F., Chen, H., Huang, J.
|
|
<strong>Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair.</strong>
|
|
Proc. Nat. Acad. Sci. 110: 10646-10651, 2013.
|
|
|
|
|
|
[PubMed: 23509288]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1220921110]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, Y., Cortez, D., Yazdi, P., Neff, N., Elledge, S. J., Qin, J.
|
|
<strong>BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures.</strong>
|
|
Genes Dev. 14: 927-939, 2000.
|
|
|
|
|
|
[PubMed: 10783165]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wechsler, T., Newman, S., West, S. C.
|
|
<strong>Aberrant chromosome morphology in human cells defective for Holliday junction resolution.</strong>
|
|
Nature 471: 642-646, 2011.
|
|
|
|
|
|
[PubMed: 21399624]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09790]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, L., Davies, S. L., North, P. S., Goulaouic, H., Riou, J.-F., Turley, H., Gatter, K. C., Hickson, I. D.
|
|
<strong>The Bloom's syndrome gene product interacts with topoisomerase III.</strong>
|
|
J. Biol. Chem. 275: 9636-9644, 2000.
|
|
|
|
|
|
[PubMed: 10734115]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.275.13.9636]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wu, L., Hickson, I. D.
|
|
<strong>The Bloom's syndrome helicase suppresses crossing over during homologous recombination.</strong>
|
|
Nature 426: 870-874, 2003.
|
|
|
|
|
|
[PubMed: 14685245]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature02253]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yankiwski, V., Marciniak, R. A., Guarente, L., Neff, N. F.
|
|
<strong>Nuclear structure in normal and Bloom syndrome cells.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 5214-5219, 2000.
|
|
|
|
|
|
[PubMed: 10779560]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.090525897]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yusa, K., Horie, K., Kondoh, G., Kouno, M., Maeda, Y., Kinoshita, T., Takeda, J.
|
|
<strong>Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.</strong>
|
|
Nature 429: 896-899, 2004.
|
|
|
|
|
|
[PubMed: 15215867]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature02646]
|
|
|
|
|
|
</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 : 10/28/2013<br>Patricia A. Hartz - updated : 8/27/2013<br>Paul J. Converse - updated : 5/3/2012<br>Ada Hamosh - updated : 6/29/2011<br>George E. Tiller - updated : 7/7/2010<br>Paul J. Converse - updated : 11/19/2008<br>George E. Tiller - updated : 5/30/2008<br>Cassandra L. Kniffin - updated : 10/10/2007<br>George E. Tiller - updated : 1/16/2007<br>Patricia A. Hartz - updated : 1/18/2005<br>Marla J. F. O'Neill - updated : 12/22/2004<br>George E. Tiller - updated : 9/2/2004<br>Ada Hamosh - updated : 7/22/2004<br>Ada Hamosh - updated : 12/30/2003<br>George E. Tiller - updated : 12/3/2003<br>Victor A. McKusick - updated : 8/27/2003<br>Patricia A. Hartz - updated : 7/7/2003<br>Ada Hamosh - updated : 2/6/2003<br>Patricia A. Hartz - updated : 1/7/2003<br>Patricia A. Hartz - updated : 12/16/2002<br>Ada Hamosh - updated : 9/30/2002<br>George E. Tiller - updated : 6/19/2001<br>Ada Hamosh - updated : 4/4/2001<br>Victor A. McKusick - updated : 3/13/2001<br>Paul J. Converse - updated : 11/16/2000<br>Ada Hamosh - updated : 8/31/2000<br>Victor A. McKusick - updated : 8/7/2000<br>Victor A. McKusick - updated : 7/26/2000<br>Victor A. McKusick - updated : 2/25/2000
|
|
</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">
|
|
Victor A. McKusick : 2/25/2000
|
|
</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 : 03/20/2024<br>carol : 08/23/2022<br>carol : 08/22/2022<br>carol : 09/30/2016<br>carol : 07/09/2016<br>carol : 6/15/2016<br>alopez : 10/28/2013<br>mgross : 8/27/2013<br>terry : 3/14/2013<br>carol : 5/24/2012<br>carol : 5/24/2012<br>mgross : 5/9/2012<br>carol : 5/8/2012<br>mgross : 5/4/2012<br>terry : 5/3/2012<br>alopez : 7/6/2011<br>terry : 6/29/2011<br>wwang : 6/24/2011<br>terry : 9/9/2010<br>alopez : 7/21/2010<br>terry : 7/7/2010<br>mgross : 11/19/2008<br>terry : 11/19/2008<br>wwang : 6/5/2008<br>terry : 5/30/2008<br>ckniffin : 2/5/2008<br>wwang : 10/16/2007<br>ckniffin : 10/10/2007<br>wwang : 1/25/2007<br>terry : 1/16/2007<br>mgross : 4/14/2005<br>mgross : 1/18/2005<br>carol : 1/12/2005<br>carol : 1/12/2005<br>terry : 12/22/2004<br>carol : 9/3/2004<br>terry : 9/2/2004<br>alopez : 7/26/2004<br>terry : 7/22/2004<br>alopez : 7/6/2004<br>alopez : 12/31/2003<br>terry : 12/30/2003<br>mgross : 12/3/2003<br>tkritzer : 8/28/2003<br>tkritzer : 8/27/2003<br>carol : 8/8/2003<br>carol : 7/10/2003<br>mgross : 7/7/2003<br>alopez : 5/29/2003<br>alopez : 5/29/2003<br>terry : 5/29/2003<br>ckniffin : 3/11/2003<br>alopez : 2/10/2003<br>alopez : 2/10/2003<br>terry : 2/6/2003<br>mgross : 1/7/2003<br>mgross : 1/7/2003<br>mgross : 1/3/2003<br>terry : 12/16/2002<br>alopez : 9/30/2002<br>tkritzer : 9/30/2002<br>carol : 1/14/2002<br>cwells : 6/20/2001<br>cwells : 6/19/2001<br>alopez : 4/5/2001<br>terry : 4/4/2001<br>cwells : 3/27/2001<br>cwells : 3/26/2001<br>terry : 3/13/2001<br>joanna : 1/17/2001<br>joanna : 1/17/2001<br>joanna : 1/17/2001<br>joanna : 1/17/2001<br>mgross : 11/16/2000<br>alopez : 9/5/2000<br>terry : 8/31/2000<br>mcapotos : 8/28/2000<br>mcapotos : 8/10/2000<br>terry : 8/7/2000<br>mcapotos : 8/1/2000<br>mcapotos : 7/26/2000<br>mcapotos : 7/26/2000<br>alopez : 7/26/2000<br>terry : 7/20/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000<br>alopez : 2/25/2000
|
|
</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>
|
|
|
|
|