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<meta name="description" content="Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, and the molecular etiology remains undiagnosed in the majority of cases. Through whole-exome sequencing, we identified recessive nonsense and splicing mutations in FBXL4 segregating in …"><meta name="keywords" content="pmid:23993193, PMC3769921, doi:10.1016/j.ajhg.2013.07.017, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Penelope E Bonnen, John W Yarham, Robert W Taylor, Acidosis, Lactic / complications, Acidosis, Lactic / genetics, Acidosis, Lactic / pathology, Base Sequence, Child, Child, Preschool, Chromosome Segregation / genetics, DNA, Mitochondrial / genetics*, Electron Transport / genetics, F-Box Proteins / chemistry, F-Box Proteins / genetics*, Female, Fibroblasts / metabolism, Fibroblasts / pathology, Gene Dosage / genetics, Genes, Recessive / genetics, Genetic Predisposition to Disease*, Humans, Infant, Infant, Newborn, Male, Mitochondrial Encephalomyopathies / complications, Mitochondrial Encephalomyopathies / genetics*, Mitochondrial Encephalomyopathies / pathology, Molecular Sequence Data, Muscle, Skeletal / pathology, Mutation / genetics*, Oxidative Phosphorylation, Pedigree, Protein Transport, Ubiquitin-Protein Ligases / chemistry, Ubiquitin-Protein Ligases / genetics*, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/23993193/"><meta property="og:description" content="Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, and the molecular etiology remains undiagnosed in the majority of cases. Through whole-exome sequencing, we identified recessive nonsense and splicing mutations in FBXL4 segregating in …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/23993193/"><meta name="twitter:description" content="Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, and the molecular etiology remains undiagnosed in the majority of cases. Through whole-exome sequencing, we identified recessive nonsense and splicing mutations in FBXL4 segregating in …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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|
||
class="search-input-link clipboard-link hidden"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="clipboard">
|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23993193%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23993193%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 23993193 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 23993193"/>
|
||
<input type="hidden" name="email-subject-hash" value="f4102fd942d66ca4a01a809e3d68da74a516715129fe0e8509233954881a2ec9"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="23993193">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(13)00337-6"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=3048&itool=Abstract-def&log$=linkouticon&uid=23993193&db=pubmed&nlmid=0370475"
|
||
title="See full text options at Elsevier Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Elsevier Science"
|
||
data-ga-label="23993193"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-celloa.png" alt="Elsevier Science full text link"><span class="text">
|
||
|
||
Elsevier Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/23993193/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=23993193&db=pubmed&nlmid=0370475"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="23993193"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/23993193/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/23993193/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="23993193" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F23993193%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="5BZ0VfiUACpjcwbWHYhmE24b0zSkmsCRmoJ5y5LgadcN6XhMkhUo8aAPyDAwf3ab"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2013 Sep 5;93(3):471-81.</span>
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Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance
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Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance
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><sup class="key">1</sup> Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. pbonnen@bcm.edu</li>
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Nuclear genetic disorders causing mitochondrial DNA (mtDNA) depletion are clinically and genetically heterogeneous, and the molecular etiology remains undiagnosed in the majority of cases. Through whole-exome sequencing, we identified recessive nonsense and splicing mutations in FBXL4 segregating in three unrelated consanguineous kindreds in which affected children present with a fatal encephalopathy, lactic acidosis, and severe mtDNA depletion in muscle. We show that FBXL4 is an F-box protein that colocalizes with mitochondria and that loss-of-function and splice mutations in this protein result in a severe respiratory chain deficiency, loss of mitochondrial membrane potential, and a disturbance of the dynamic mitochondrial network and nucleoid distribution in fibroblasts from affected individuals. Expression of the wild-type FBXL4 transcript in cell lines from two subjects fully rescued the levels of mtDNA copy number, leading to a correction of the mitochondrial biochemical deficit. Together our data demonstrate that mutations in FBXL4 are disease causing and establish FBXL4 as a mitochondrial protein with a possible role in maintaining mtDNA integrity and stability.
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Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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<div class="figure-caption-contents"><p> Genetic Investigation of the Families… </p></div>
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<div class="figure-caption-contents"><p> Genetic Investigation of the Families Confirms Segregation with Disease of Recessive <i> FBXL4 </i> Mutations… </p></div>
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<div class="figure-caption-contents">Genetic Investigation of the Families Confirms Segregation with Disease of Recessive <i>FBXL4</i> Mutations The pedigrees of S1 (A), S2 (B), and S3 (C) are shown, highlighting the consanguineous nature of each family. The probands are indicated by black arrows, and all individuals presenting with similar clinical features are shown as filled black symbols (pedigrees are drawn to accepted standards<sup>37</sup>). A sequencing chromatogram obtained by targeted resequencing is shown for each proband, confirming the presence of the c.1555C>T (p.Gln519<sup>∗</sup>) (S1), c.1303C>T (p.Arg435<sup>∗</sup>) (S2), and c.1703G>CGC (S3) mutations.</div>
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<div class="figure-caption-contents"><p> FBXL4 Protein Structure and Localization… </p></div>
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<div class="figure-caption-contents"><p> FBXL4 Protein Structure and Localization (A) Schematic of FBXL4 showing the location of… </p></div>
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<div class="figure-caption-contents">FBXL4 Protein Structure and Localization (A) Schematic of FBXL4 showing the location of the bioinformatically determined mitochondrial localization sequence (mt) and conserved domains (F-box CDD ID pfam12937, AMN1 CDD ID cd09293). The locations of each of the mutations are indicated. (B) Three-dimensional structural modeling of FBXL4 shows the canonical folds of the F-box and nine leucine-rich repeats. The protein schematic and 3D structure are both displayed in reverse rainbow from the N to C terminus. (C) Splicing of exon 9 was demonstrated to be significantly impaired in S3 compared to controls. Error bars indicate standard deviation; <sup>∗∗∗</sup>p < 0.0001. (D) FBXL4 was confirmed to be a mitochondrial protein through an immunolocalization study in human fibroblasts, showing HA-tagged FBXL4 (green) colocalizing with MitoTracker Red-labeled mitochondria. Nuclei were counterstained with DAPI (blue).</div>
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<div class="figure-caption-contents"><p> Individuals with <i> FBXL4 </i> Mutations Display… </p></div>
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<div class="figure-caption-contents"><p> Individuals with <i> FBXL4 </i> Mutations Display Mitochondrial Biochemical Dysfunction (A) Cytochrome c oxidase (COX)… </p></div>
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<div class="figure-caption-contents">Individuals with <i>FBXL4</i> Mutations Display Mitochondrial Biochemical Dysfunction (A) Cytochrome c oxidase (COX) histocytochemical activities in skeletal muscle from S1 and S2 are globally decreased in comparison to control muscle, although somewhat unusually there are occasional, COX-positive fibers in S1 showing discrete, punctate enzyme activity. (B and C) Respiratory chain complex biochemical activity was determined in both skeletal muscle (B) and fibroblasts (C) from all probands (dark gray columns, S1; light gray columns, S2; white columns, S3) and is shown relative to the mean activity measured in 25 controls. (D) Mitochondrial membrane potential was measured in fibroblasts from S1, S2, and S3 together with seven controls (C). Cells from each affected individual showed severely compromised membrane potential compared to controls. <sup>∗∗∗</sup>p < 0.0001. (E) Severe depletion of mtDNA was determined in skeletal muscle and fibroblasts from each of the three probands (dark gray columns, S1; light gray columns, S2; white columns, S3) when measured in comparison to age-matched control muscle (n = 20) and fibroblasts (n = 3) (black columns). For all data, error bars indicate standard deviation.</div>
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<p> Figure 4 </p>
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</strong>
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<div class="figure-caption-contents"><p> Characterization of the OXPHOS Defects… </p></div>
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<p> Figure 4 </p>
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<div class="figure-caption-contents"><p> Characterization of the OXPHOS Defects in Fibroblasts (A) Microscale oxygraphy analysis of live… </p></div>
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Figure 4
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<div class="figure-caption-contents">Characterization of the OXPHOS Defects in Fibroblasts (A) Microscale oxygraphy analysis of live fibroblasts demonstrated a profound respiratory deficiency in cells from both S1 (c.1555C>T [p.Gln519<sup>∗</sup>], n = 22, white triangles) and S2 (c.1303C>T [p.Arg435<sup>∗</sup>], n = 14, white circles), compared to the combined data of control cell lines (n = 5, black squares). Error bars indicate the standard deviation. (B) The total amount of ATP produced by fibroblasts from S1 and S2 is not dramatically different to controls, but the proportion contributed by OXPHOS (black columns) is significantly reduced, whereas that contributed by glycolysis (white columns) is significantly increased. (C) The ability of fibroblasts from S1 and S2 to respond to stress, as measured by the spare respiratory capacity (maximal OCR minus basal OCR), is significantly reduced in comparison to controls. <sup>∗∗∗</sup>p < 0.0001. (D) The efficiency of the coupling of respiration to ATP synthesis (oligomycin-sensitive OCR as a percent of basal OCR) was significantly impaired in fibroblasts from S2 but not S1 compared to controls. For all data, error bars indicate standard deviation. <sup>∗∗∗</sup>p < 0.0001; NS, not significant. (E) Immunoblotting for protein components of each of the mitochondrial respiratory chain complexes was completed in S1 and S2 to determine their abundance relative to control (labeled C). Three subunits of complex I (NDUFA13, NDUFB8, and NDUFA9), one of complex II (SDHA), one of complex III (UQCRC2), three of complex IV (COXI, COXII, and COXIV), and one of complex V (ATPB) were probed, with TOMM20 as a mitochondrial marker and β-actin as a loading control.</div>
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<p> Figure 5 </p>
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<div class="figure-caption-contents"><p> Mitochondrial Network and Nucleoid Morphology… </p></div>
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<p> Figure 5 </p>
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<div class="figure-caption-contents"><p> Mitochondrial Network and Nucleoid Morphology Is Disrupted in Individuals with <i> FBXL4 </i> Mutations The… </p></div>
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Figure 5
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<div class="figure-caption-contents">Mitochondrial Network and Nucleoid Morphology Is Disrupted in Individuals with <i>FBXL4</i> Mutations The upper panels show representative images of MitoTracker Red staining of control (left), S1 (middle), and S2 (right) fibroblasts. Note fragmentation and shortening of mitochondria in both these cell lines compared to the control. The lower panels show nucleoid staining by PicoGreen, revealing larger nucleoids with perinuclear clustering in cells from both subjects.</div>
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<p> Figure 6 </p>
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<div class="figure-caption-contents"><i> FBXL4 </i> Gene Rescue Studies in…</div>
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<strong class="figure-label">
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<p> Figure 6 </p>
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<div class="figure-caption-contents"><i> FBXL4 </i> Gene Rescue Studies in S1 and S2 Cells Fibroblasts were transduced with…</div>
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Figure 6
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<div class="figure-caption-contents"><i>FBXL4</i> Gene Rescue Studies in S1 and S2 Cells Fibroblasts were transduced with either <i>GFP</i> (black columns) or wild-type <i>FBXL4</i> (gray columns) and compared to transduced control fibroblasts. (A–C) mtDNA copy number (A), complex IV activity (B), and membrane potential (C) were recovered to normal levels in S1 and S2 fibroblasts transfected with wild-type FBXL4 but not GFP. (D) FBXL4 mRNA levels were increased in control (C) and S1 and S2 fibroblasts infected with wild-type FBXL4 but not in those infected with <i>GFP</i>. Transcript levels are reported relative to <i>GAPDH</i>. For all graphs, error bars indicate standard deviation; <sup>∗∗∗</sup>p < 0.0001, <sup>∗∗</sup>p < 0.01.</div>
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Koopman W.J.H., Willems P.H.G.M., Smeitink J.A.M. Monogenic mitochondrial disorders. N. Engl. J. Med. 2012;366:1132–1141.
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|
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Research Support, N.I.H., Extramural"[pt]"
|
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data-ga-category="search"
|
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data-ga-action="add_to_search"
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data-ga-label=""Research Support, N.I.H., Extramural"[pt]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Research Support, Non-U.S. Gov't"
|
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tabindex="0"
|
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aria-controls="keyword-actions-publication-types-1"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Research Support, Non-U.S. Gov't
|
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</button><div id="keyword-actions-publication-types-1"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Research Support, Non-U.S. Gov't"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Research+Support%2C+Non-U.S.+Gov%27t%22%5Bpt%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Research+Support%2C+Non-U.S.+Gov%27t%22%5Bpt%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Research Support, Non-U.S. Gov't"[pt]"
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data-ga-action="pub_type"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Research+Support%2C+Non-U.S.+Gov%27t"
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data-ga-category="search_mesh"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
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</a></li></ul></div></div></div></li></ul>
|
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</div>
|
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|
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|
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|
||
|
||
|
||
<div id="mesh-terms" class="mesh-terms keywords-section">
|
||
<h2 class="title">
|
||
MeSH terms
|
||
</h2>
|
||
|
||
<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Acidosis, Lactic / complications"
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aria-expanded="false"
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Acidosis, Lactic / complications
|
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</button><div id="keyword-actions-mesh-terms-0"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Acidosis, Lactic / complications"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Acidosis%2C+Lactic%2Fcomplications%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Acidosis%2C+Lactic%2Fcomplications%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Acidosis, Lactic/complications"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Acidosis%2C+Lactic"
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data-ga-category="search_mesh"
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Acidosis, Lactic / genetics"
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aria-expanded="false"
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data-pinger-ignore>
|
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Acidosis, Lactic / genetics
|
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</button><div id="keyword-actions-mesh-terms-1"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Acidosis, Lactic / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Acidosis%2C+Lactic%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Acidosis%2C+Lactic%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Acidosis, Lactic/genetics"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Acidosis, Lactic/genetics"[MeSH]"
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data-ga-label=""Acidosis, Lactic/genetics"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Acidosis, Lactic / pathology"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-2"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Acidosis, Lactic / pathology
|
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</button><div id="keyword-actions-mesh-terms-2"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Acidosis, Lactic / pathology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Acidosis%2C+Lactic%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Acidosis%2C+Lactic%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Acidosis, Lactic/pathology"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Acidosis, Lactic/pathology"[MeSH]"
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data-ga-category="search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Base Sequence"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-3"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Base Sequence
|
||
</button><div id="keyword-actions-mesh-terms-3"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Base Sequence"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Base+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Base+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Base Sequence"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Base Sequence">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Base+Sequence"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Base Sequence">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
|
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role="button"
|
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data-search-term=""Base Sequence"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Base Sequence"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Child"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-4"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Child
|
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</button><div id="keyword-actions-mesh-terms-4"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Child"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Child%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Child%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Child"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Child">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Child"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Child">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Child"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Child"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Child, Preschool"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-5"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Child, Preschool
|
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</button><div id="keyword-actions-mesh-terms-5"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Child, Preschool"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Child%2C+Preschool%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Child%2C+Preschool%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Child, Preschool"[MeSH]"
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data-ga-action="mesh_term"
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data-ga-label="Child, Preschool">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Child%2C+Preschool"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Child, Preschool">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Child, Preschool"[MeSH]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Child, Preschool"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Chromosome Segregation / genetics"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-6"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Chromosome Segregation / genetics
|
||
</button><div id="keyword-actions-mesh-terms-6"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Chromosome Segregation / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Chromosome+Segregation%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Chromosome+Segregation%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Chromosome Segregation/genetics"[MeSH]"
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data-ga-action="mesh_term"
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data-ga-label="Chromosome Segregation / genetics">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Chromosome+Segregation"
|
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Chromosome Segregation / genetics">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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role="button"
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data-search-term=""Chromosome Segregation/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Chromosome Segregation/genetics"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
|
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aria-label="Toggle dropdown menu for keyword DNA, Mitochondrial / genetics*"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-7"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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DNA, Mitochondrial / genetics*
|
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</button><div id="keyword-actions-mesh-terms-major-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword DNA, Mitochondrial / genetics*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22DNA%2C+Mitochondrial%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22DNA%2C+Mitochondrial%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="DNA, Mitochondrial/genetics"[MAJR]"
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data-ga-action="mesh_term"
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data-ga-label="DNA, Mitochondrial / genetics*">
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=DNA%2C+Mitochondrial"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="DNA, Mitochondrial / genetics*">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""DNA, Mitochondrial/genetics"[MAJR]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Electron Transport / genetics"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-8"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Electron Transport / genetics
|
||
</button><div id="keyword-actions-mesh-terms-8"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Electron Transport / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Electron+Transport%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Electron+Transport%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Electron Transport/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Electron Transport / genetics">
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Electron+Transport"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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data-ga-label="Electron Transport / genetics">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
|
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role="button"
|
||
data-search-term=""Electron Transport/genetics"[MeSH]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Electron Transport/genetics"[MeSH]"
|
||
href="#">
|
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Add to Search
|
||
</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword F-Box Proteins / chemistry"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-9"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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F-Box Proteins / chemistry
|
||
</button><div id="keyword-actions-mesh-terms-9"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword F-Box Proteins / chemistry"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22F-Box+Proteins%2Fchemistry%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22F-Box+Proteins%2Fchemistry%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="F-Box Proteins/chemistry"[MeSH]"
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data-ga-label="F-Box Proteins / chemistry">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=F-Box+Proteins"
|
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data-ga-category="search_mesh"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""F-Box Proteins/chemistry"[MeSH]"
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data-ga-category="search"
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data-ga-label=""F-Box Proteins/chemistry"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword F-Box Proteins / genetics*"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-major-10"
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aria-expanded="false"
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data-pinger-ignore>
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F-Box Proteins / genetics*
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</button><div id="keyword-actions-mesh-terms-major-10"
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hidden
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aria-label="Dropdown menu for keyword F-Box Proteins / genetics*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22F-Box+Proteins%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22F-Box+Proteins%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="F-Box Proteins/genetics"[MAJR]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=F-Box+Proteins"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
|
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role="button"
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data-search-term=""F-Box Proteins/genetics"[MAJR]"
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data-ga-category="search"
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data-ga-label=""F-Box Proteins/genetics"[MAJR]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Female"
|
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-11"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Female
|
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</button><div id="keyword-actions-mesh-terms-11"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Female"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Female"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Female"
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data-ga-category="search_mesh"
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data-ga-label="Female">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Female"[MeSH]"
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data-ga-category="search"
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data-ga-label=""Female"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Fibroblasts / metabolism"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-12"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Fibroblasts / metabolism
|
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</button><div id="keyword-actions-mesh-terms-12"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Fibroblasts / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Fibroblasts%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Fibroblasts%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Fibroblasts/metabolism"[MeSH]"
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Search in PubMed
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Fibroblasts"
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data-search-term=""Fibroblasts/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Fibroblasts / pathology"
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tabindex="0"
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aria-controls="keyword-actions-mesh-terms-13"
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aria-expanded="false"
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data-pinger-ignore>
|
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Fibroblasts / pathology
|
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</button><div id="keyword-actions-mesh-terms-13"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Fibroblasts / pathology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Fibroblasts%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Fibroblasts%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Fibroblasts/pathology"[MeSH]"
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data-ga-label="Fibroblasts / pathology">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Fibroblasts"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Fibroblasts/pathology"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Fibroblasts/pathology"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Gene Dosage / genetics"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-14"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Gene Dosage / genetics
|
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</button><div id="keyword-actions-mesh-terms-14"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Gene Dosage / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Gene+Dosage%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Gene+Dosage%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Gene Dosage/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Gene Dosage / genetics">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Gene+Dosage"
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Gene Dosage/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Genes, Recessive / genetics"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-15"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Genes, Recessive / genetics
|
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</button><div id="keyword-actions-mesh-terms-15"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Genes, Recessive / genetics"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Genes%2C+Recessive%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Genes%2C+Recessive%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Genes, Recessive/genetics"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Genes%2C+Recessive"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Genes, Recessive/genetics"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Genes, Recessive/genetics"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
|
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aria-label="Toggle dropdown menu for keyword Genetic Predisposition to Disease*"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-major-16"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Genetic Predisposition to Disease*
|
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</button><div id="keyword-actions-mesh-terms-major-16"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Genetic Predisposition to Disease*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Genetic+Predisposition+to+Disease%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Genetic+Predisposition+to+Disease%22%5BMAJR%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Genetic Predisposition to Disease"[MAJR]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Genetic+Predisposition+to+Disease"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
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data-search-term=""Genetic Predisposition to Disease"[MAJR]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Genetic Predisposition to Disease"[MAJR]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
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aria-label="Toggle dropdown menu for keyword Humans"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-17"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Humans
|
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</button><div id="keyword-actions-mesh-terms-17"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Humans"[MeSH]"
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data-ga-category="search"
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data-ga-action="mesh_term"
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data-ga-label="Humans">
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Humans"
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data-ga-category="search_mesh"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Humans"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Infant"
|
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tabindex="0"
|
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aria-controls="keyword-actions-mesh-terms-18"
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Infant
|
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</button><div id="keyword-actions-mesh-terms-18"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Infant"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Infant%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Infant%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Infant"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Infant"
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data-ga-category="search_mesh"
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data-ga-label="Infant">
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Infant"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Infant"[MeSH]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Infant, Newborn"
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tabindex="0"
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data-pinger-ignore>
|
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Infant, Newborn
|
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</button><div id="keyword-actions-mesh-terms-19"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Infant, Newborn"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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||
href="/?term=%22Infant%2C+Newborn%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Infant%2C+Newborn%22%5BMeSH%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Infant, Newborn"[MeSH]"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Male"
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aria-expanded="false"
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|
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Male
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class="keyword-actions-dropdown dropdown dropdown-container"
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aria-label="Dropdown menu for keyword Male"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Male"[MeSH]"
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Mitochondrial Encephalomyopathies / complications
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</button><div id="keyword-actions-mesh-terms-21"
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hidden
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aria-label="Dropdown menu for keyword Mitochondrial Encephalomyopathies / complications"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Mitochondrial+Encephalomyopathies%2Fcomplications%22%5BMeSH%5D&sort=date&sort_order=desc"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Mitochondrial Encephalomyopathies / genetics*
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Mitochondrial Encephalomyopathies / pathology
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aria-label="Dropdown menu for keyword Mitochondrial Encephalomyopathies / pathology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Mitochondrial+Encephalomyopathies%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Mitochondrial Encephalomyopathies/pathology"[MeSH]"
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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data-pinger-ignore>
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Molecular Sequence Data
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</button><div id="keyword-actions-mesh-terms-24"
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|
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aria-label="Dropdown menu for keyword Molecular Sequence Data"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Molecular+Sequence+Data%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Molecular Sequence Data"[MeSH]"
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|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-expanded="false"
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Muscle, Skeletal / pathology
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data-href="/?term=%22Muscle%2C+Skeletal%2Fpathology%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Muscle, Skeletal/pathology"[MeSH]"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Mutation / genetics*
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</button><div id="keyword-actions-mesh-terms-major-26"
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hidden
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data-search-term=""Mutation/genetics"[MAJR]"
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data-ga-category="search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Oxidative Phosphorylation"
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Oxidative Phosphorylation
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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data-pinger-ignore>
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Pedigree
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Protein Transport"
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Protein Transport
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|
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<div id="supplementary-concepts" class="supplementary-concepts keywords-section">
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Supplementary concepts
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<div id="related-links" class="related-links">
|
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<h2 class="title">
|
||
Related information
|
||
</h2>
|
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|
||
<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&from_uid=23993193"
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=1">
|
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Cited in Books
|
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</a></li><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&from_uid=23993193"
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ClinVar
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</a></li><li><a title="Link to related CDD entry" href="https://www.ncbi.nlm.nih.gov/cdd?linkname=pubmed_cdd&from_uid=23993193"
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Domains
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</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&from_uid=23993193"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=4">
|
||
Gene
|
||
</a></li><li><a title="Link to Gene for the GeneRIF subcategory" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene_rif&from_uid=23993193"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=5">
|
||
Gene (GeneRIF)
|
||
</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=23993193"
|
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=6">
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MedGen
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</a></li><li><a title="Related records in MedGen based on citations in GeneReviews and Medical Genetics Summaries" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen_bookshelf_cited&from_uid=23993193"
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=7">
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MedGen (Bookshelf cited)
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</a></li><li><a title="OMIM (cited) Links" href="https://www.ncbi.nlm.nih.gov/omim?linkname=pubmed_omim_cited&from_uid=23993193"
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|
||
OMIM (cited)
|
||
</a></li><li><a title="Published protein sequences" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein&from_uid=23993193"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=9">
|
||
Protein
|
||
</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=23993193"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=10">
|
||
Protein (RefSeq)
|
||
</a></li><li><a title="PubMed to SNP links" href="https://www.ncbi.nlm.nih.gov/snp?linkname=pubmed_snp&from_uid=23993193"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=23993193&ordinalpos=1&linkpos=11">
|
||
SNP
|
||
</a></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
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<div id="grants" class="grants">
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<h2 class="title">
|
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Grants and funding
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</h2>
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<div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a
|
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title="All articles for grant CA125123/CA/NCI NIH HHS/United States"
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