3152 lines
223 KiB
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- *608059 - HES FAMILY bHLH TRANSCRIPTION FACTOR 7; HES7
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- OMIM
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<p>
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<span class="h4">*608059</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608059">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000179111;t=ENST00000541682" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=84667" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=608059" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000179111;t=ENST00000541682" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001165967,NM_032580,XM_047436940,XM_047436941,XM_047436942" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001165967" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=608059" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=09729&isoform_id=09729_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/HES7" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/13383231,119610498,145207994,260166650,296434525,2217314384,2217314386,2217314388,2462558298,2462558300,2462558302" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/Q9BYE0" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=84667" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000179111;t=ENST00000541682" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=HES7" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=HES7" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+84667" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/HES7" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:84667" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/84667" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr17&hgg_gene=ENST00000541682.7&hgg_start=8120592&hgg_end=8126634&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608059[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608059[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000179111" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=HES7" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=HES7" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=HES7" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HES7&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA29254" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:15977" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2135679" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/HES7#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:2135679" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/84667/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/results?search_type=advanced&omia_id=001944,001987" class="mim-tip-hint" title="OMIA" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OMIA', 'domain': 'omia.angis.org.au'})">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=84667" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-980526-125" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:84667" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=HES7&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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608059
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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HES FAMILY bHLH TRANSCRIPTION FACTOR 7; HES7
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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HAIRY/ENHANCER OF SPLIT, DROSOPHILA, HOMOLOG OF, 7
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HES7" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HES7</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/17/193?start=-3&limit=10&highlight=193">17p13.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:8120592-8126634&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">17:8,120,592-8,126,634</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/17/193?start=-3&limit=10&highlight=193">
|
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17p13.1
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
Spondylocostal dysostosis 4, autosomal recessive
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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|
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<a href="/entry/613686"> 613686 </a>
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/608059" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/608059" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
|
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>HES7 encodes a basic helix-loop-helix-Orange domain transcriptional repressor protein that is both a direct target of the Notch signaling pathway (see <a href="/entry/190198">190198</a>) and part of a negative feedback mechanism required to attenuate Notch signaling (summary by <a href="#8" class="mim-tip-reference" title="Sparrow, D. B., Guillen-Navarro, E., Fatkin, D., Dunwoodie, S. L. <strong>Mutation of hairy-and-enhancer-of-split-7 in humans causes spondylocostal dysostosis.</strong> Hum. Molec. Genet. 17: 3761-3766, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775957</a>] [<a href="https://doi.org/10.1093/hmg/ddn272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18775957">Sparrow et al., 2008</a>) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18775957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Bessho, Y., Miyoshi, G., Sakata, R., Kageyama, R. <strong>Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm.</strong> Genes Cells 6: 175-185, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260262</a>] [<a href="https://doi.org/10.1046/j.1365-2443.2001.00409.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11260262">Bessho et al. (2001)</a> cloned mouse Hes7 and, by EST database searching and PCR, obtained a cDNA encoding human HES7. The deduced mouse and human proteins contain 225 amino acids, and both have an N-terminal basic helix-loop-helix (bHLH) domain, a central 'orange' domain, and a conserved C-terminal WRPW sequence. Human and mouse HES7 are identical in the bHLH domain and share 90.7% amino acid identity overall. Compared with other mouse HES proteins, Hes7 is most similar to Hes5 (<a href="/entry/607348">607348</a>), particularly in the bHLH and orange domains. Northern blot analysis of day-9.5 mouse embryos detected a 1.0-kb Hes7 transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11260262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Bessho, Y., Miyoshi, G., Sakata, R., Kageyama, R. <strong>Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm.</strong> Genes Cells 6: 175-185, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260262</a>] [<a href="https://doi.org/10.1046/j.1365-2443.2001.00409.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11260262">Bessho et al. (2001)</a> determined that mouse Hes7 contains 4 exons and spans about 3 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11260262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 12/18/2013."None>Gross (2013)</a> mapped the HES7 gene to chromosome 17p13.1 based on an alignment of the HES7 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AB049064" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AB049064</a>) with the genomic sequence (GRCh37).</p><p><a href="#1" class="mim-tip-reference" title="Bessho, Y., Miyoshi, G., Sakata, R., Kageyama, R. <strong>Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm.</strong> Genes Cells 6: 175-185, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260262</a>] [<a href="https://doi.org/10.1046/j.1365-2443.2001.00409.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11260262">Bessho et al. (2001)</a> mapped the mouse Hes7 gene to chromosome 11, next to the Aloxe3 gene (<a href="/entry/607206">607206</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11260262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By in situ hybridization of day-8.5 through day-12.0 mouse embryos, <a href="#1" class="mim-tip-reference" title="Bessho, Y., Miyoshi, G., Sakata, R., Kageyama, R. <strong>Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm.</strong> Genes Cells 6: 175-185, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260262</a>] [<a href="https://doi.org/10.1046/j.1365-2443.2001.00409.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11260262">Bessho et al. (2001)</a> found dynamic expression of Hes7 in the presomitic mesoderm (PSM). Transfection experiments determined that mouse Hes7 repressed transcription from N box- and E box-containing promoters. Hes7 also suppressed E47 (<a href="/entry/147141">147141</a>)-induced transcriptional activation. Promoter analysis indicated that mouse Hes7 expression was controlled by Notch signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11260262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>During somitogenesis, a pair of somites buds off from the PSM every 2 hours in mouse embryos, suggesting that somite segmentation is controlled by a biologic clock with a 2-hour cycle. Expression of Hes7, an effector of Notch signaling, follows a 2-hour oscillatory cycle controlled by negative feedback; it had been proposed that this is the molecular basis for the somite segmentation clock. To address the biologic importance of Hes7 instability, <a href="#4" class="mim-tip-reference" title="Hirata, H., Bessho, Y., Kokubu, H., Masamizu, Y., Yamada, S., Lewis, J., Kageyama, R. <strong>Instability of Hes7 protein is crucial for the somite segmentation clock.</strong> Nature Genet. 36: 750-754, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15170214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15170214</a>] [<a href="https://doi.org/10.1038/ng1372" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15170214">Hirata et al. (2004)</a> generated mice expressing mutant Hes7 with a longer half-life but normal repressor activity. In these mice, somite segmentation and oscillatory expression became severely disorganized after a few normal cycles of segmentation. <a href="#4" class="mim-tip-reference" title="Hirata, H., Bessho, Y., Kokubu, H., Masamizu, Y., Yamada, S., Lewis, J., Kageyama, R. <strong>Instability of Hes7 protein is crucial for the somite segmentation clock.</strong> Nature Genet. 36: 750-754, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15170214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15170214</a>] [<a href="https://doi.org/10.1038/ng1372" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15170214">Hirata et al. (2004)</a> simulated this effect mathematically using a direct autorepression model. Thus, instability of Hes7 is essential for sustained oscillation and for its function as a segmentation clock. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15170214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Diaz-Cuadros, M., Wagner, D. E., Budjan, C., Hubaud, A., Tarazona, O. A., Donelly, S., Michaut, A., Al Tanoury, Z., Yoshioka-Kobayashi, K., Niino, Y., Kageyama, R., Miyawaki, A., Touboul, J., Pourguie, O. <strong>In vitro characterization of the human segmentation clock.</strong> Nature 580: 113-118, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31915384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31915384</a>] [<a href="https://doi.org/10.1038/s41586-019-1885-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31915384">Diaz-Cuadros et al. (2020)</a> showed that human and mouse PSM cells derived in vitro recapitulated the oscillations of the segmentation clock, as measured by expression of fluorescence-tagged HES7. Human PSM cells oscillated with a period 2 times longer than that of mouse cells (5 vs 2.5 hours, respectively), but were similarly regulated by FGF (see <a href="/entry/131220">131220</a>), Wnt (see <a href="/entry/606359">606359</a>), Notch, and YAP (YAP1; <a href="/entry/606608">606608</a>) signaling. Single-cell RNA sequencing revealed that mouse and human PSM cells in vitro followed a developmental trajectory similar to that of mouse PSM cells in vivo. Furthermore, <a href="#2" class="mim-tip-reference" title="Diaz-Cuadros, M., Wagner, D. E., Budjan, C., Hubaud, A., Tarazona, O. A., Donelly, S., Michaut, A., Al Tanoury, Z., Yoshioka-Kobayashi, K., Niino, Y., Kageyama, R., Miyawaki, A., Touboul, J., Pourguie, O. <strong>In vitro characterization of the human segmentation clock.</strong> Nature 580: 113-118, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31915384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31915384</a>] [<a href="https://doi.org/10.1038/s41586-019-1885-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31915384">Diaz-Cuadros et al. (2020)</a> demonstrated that FGF signaling controlled the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in 'clock and wavefront' models. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31915384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Yoshioka-Kobayashi, K., Matsumiya, M., Niino, Y., Isomura, A., Kori, H., Miyawaki, A., Kageyama, R. <strong>Coupling delay controls synchronized oscillation in the segmentation clock.</strong> Nature 580: 119-123, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31915376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31915376</a>] [<a href="https://doi.org/10.1038/s41586-019-1882-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31915376">Yoshioka-Kobayashi et al. (2020)</a> established a live-imaging system in which a fluorescent reporter was fused to Hes7 to monitor synchronous oscillations in Hes7 expression in mouse PSM at single-cell resolution. They found that wildtype PSM cells could rapidly correct for phase fluctuations in Hes7 oscillations, whereas loss of the Notch modulator Lfng (<a href="/entry/602576">602576</a>) led to loss of synchrony between PSM cells. Moreover, Hes7 oscillations were severely dampened in individual cells of Lfng-null PSM. When Lfng-null PSM cells were completely dissociated, the amplitude and periodicity of Hes7 oscillations were almost normal, suggesting that Lfng is involved mostly in cell-cell coupling. Mixed cultures of wildtype and Lfng-null PSM cells, and an optogenetic Notch signaling reporter assay, revealed that Lfng delayed the signal-sending process of intercellular Notch signaling transmission. These results, as well as mathematical modeling, suggested that Lfng-null PSM cells shortened the coupling delay, thereby approaching oscillation or amplitude death of coupled oscillators. A small compound that lengthened the coupling delay partially rescued the amplitude and synchrony of Hes7 oscillations in Lfng-null PSM cells. The findings revealed a delay control mechanism of the oscillatory networks involved in somite segmentation and showed that intercellular coupling with the correct delay is essential for synchronized oscillation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31915376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Matsuda, M., Yamanaka, Y., Uemura, M., Osawa, M., Saito, M. K., Nagahashi, A., Nishio, M., Guo, L., Ikegawa, S., Sakurai, S., Kihara, S., Maurissen, T. L., and 10 others. <strong>Recapitulating the human segmentation clock with pluripotent stem cells.</strong> Nature 580: 124-129, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32238941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32238941</a>] [<a href="https://doi.org/10.1038/s41586-020-2144-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32238941">Matsuda et al. (2020)</a> used human induced pluripotent stem cells for in vitro induction of PSM and its derivatives to model human somitogenesis, with a focus on the human segmentation clock. The authors observed oscillatory expression of core segmentation clock genes, including HES7 and DKK1 (<a href="/entry/605189">605189</a>), determined the period of the human segmentation clock to be around 5 hours, and demonstrated the presence of dynamic traveling wave-like gene expression in in vitro-induced human PSM. Identification and comparison of oscillatory genes in human and mouse PSM derived from pluripotent stem cells revealed species-specific and shared molecular components and pathways associated with the putative mouse and human segmentation clocks. Knockout of genes mutated in patients with segmentation defects of vertebrae, including HES7, LFNG, DLL3 (<a href="/entry/602768">602768</a>), and MESP2 (<a href="/entry/605195">605195</a>), followed by analysis of patient-like and patient-derived induced pluripotent stem cells revealed gene-specific alterations in oscillation, synchronization, or differentiation properties. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32238941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To investigate interspecies differences in the time scale of development, <a href="#5" class="mim-tip-reference" title="Matsuda, M., Hayashi, H., Garcia-Ojalvo, J., Yoshioka-Kobayashi, K., Kageyama, R., Yamanaka, Y., Ikeya, M., Toguchida, J., Alev, C., Ebisuya, M. <strong>Species-specific segmentation clock periods are due to differential biochemical reaction speeds.</strong> Science 369: 1450-1455, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32943519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32943519</a>] [<a href="https://doi.org/10.1126/science.aba7668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32943519">Matsuda et al. (2020)</a> recapitulated murine and human segmentation clocks displaying 2- to 3-hour and 5- to 6-hour oscillation periods, respectively. Interspecies genome-swapping analyses showed that the period difference was not due to sequence differences in HES7. Instead, multiple biochemical reactions of HES7, including degradation and expression delays, were slower in human cells than in mouse cells. With the measured biochemical parameters, the authors built a mathematical model accounting for the 2- to 3-fold period difference between the species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32943519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the proband of a consanguineous family of Caucasian Mediterranean origin with spondylocostal dysostosis mapping to chromosome 17p13 (SCDO4; <a href="/entry/613686">613686</a>), <a href="#8" class="mim-tip-reference" title="Sparrow, D. B., Guillen-Navarro, E., Fatkin, D., Dunwoodie, S. L. <strong>Mutation of hairy-and-enhancer-of-split-7 in humans causes spondylocostal dysostosis.</strong> Hum. Molec. Genet. 17: 3761-3766, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775957</a>] [<a href="https://doi.org/10.1093/hmg/ddn272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18775957">Sparrow et al. (2008)</a> identified homozygosity for a missense mutation in the HES7 gene (R25W; <a href="#0001">608059.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18775957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a brother and sister with SCDO from a nonconsanguineous Italian family, <a href="#9" class="mim-tip-reference" title="Sparrow, D. B., Sillence, D., Wouters, M. A., Turnpenny, P. D., Dunwoodie, S. L. <strong>Two novel missense mutations in hairy-and-enhancer-of-split-7 in a family with spondylocostal dysostosis.</strong> Europ. J. Hum. Genet. 18: 674-679, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20087400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20087400</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20087400[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2009.241" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20087400">Sparrow et al. (2010)</a> sequenced the 4 genes known to cause SCDO and identified compound heterozygosity for missense mutations in the HES7 gene (<a href="#0002">608059.0002</a> and <a href="#0003">608059.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20087400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 7 patients from 3 families with SCDO, <a href="#7" class="mim-tip-reference" title="Sparrow, D. B., Faqeih, E. A., Sallout, B., Alswaid, A., Ababneh, F., Al-Sayed, M., Rukban, H., Eyaid, W. M., Kageyama, R., Ellard, S., Turnpenny, P. D., Dunwoodie, S. L. <strong>Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus.</strong> Am. J. Med. Genet. 161A: 2244-2249, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23897666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23897666</a>] [<a href="https://doi.org/10.1002/ajmg.a.36073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23897666">Sparrow et al. (2013)</a> identified a homozygous frameshift mutation in the HES7 gene (<a href="#0004">608059.0004</a>) that resulted in significant reduction of HES7 protein function. Four patients were from a consanguineous Arab family and the other patients were from 2 additional families from the same geographic area. Three patients also had dextrocardia with situs inversus and 2 patients also had neural tube defects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23897666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Cats with variably shortened and/or kinked tails are widespread in Southeast Asia and southern China. <a href="#10" class="mim-tip-reference" title="Xu, X., Sun, X., Hu, X.-S., Zhuang, Y., Liu, Y.-C., Meng, H., Miao, L., Yu, H., Luo, S.-J. <strong>Whole genome sequencing identifies a missense mutation in HES7 associated with short tails in Asian domestic cats.</strong> Sci. Rep. 6: 31583, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27560986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27560986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27560986[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep31583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27560986">Xu et al. (2016)</a> established a 2-generation pedigree of 13 cats in which the dam appeared to be heterozygous for a tail with medium kink and the sire was wildtype. Radiography revealed that wildtype cats had 22 caudal vertebrae with no sign of deformity, whereas the kinked-tail dam and affected offspring exhibited reduced number of vertebrae and variable deformity, including hemivertebrae and block caudal vertebrae. Linkage analysis and whole-genome sequencing revealed that tail shortening and kinking was due to a c.5T-C transition in Hes7, resulting in a val2-to-ala (V2A) substitution. Val2 lies upstream of the bHLH domain and is completely conserved in vertebrates. In an extended sampling of 245 unrelated cats, the authors found that a significant number with shortened and/or kinked tails carried the Hes7 mutation. The results suggested that V2A is strongly associated with short/kinked tail with a dominant mode of inheritance. Cats homozygous for the V2A mutation showed tails with extreme kink, whereas heterozygotes had either minor or medium kink, suggesting a dose effect of V2A on tail morphology. No wildtype cats carried the mutation. Other than the tail abnormality, feral cats heterozygous or homozygous for V2A appeared normal and had no apparent health hazards. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27560986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the proband of a consanguineous family of Caucasian Mediterranean origin with spondylocostal dysostosis (SCDO4; <a href="/entry/613686">613686</a>), <a href="#8" class="mim-tip-reference" title="Sparrow, D. B., Guillen-Navarro, E., Fatkin, D., Dunwoodie, S. L. <strong>Mutation of hairy-and-enhancer-of-split-7 in humans causes spondylocostal dysostosis.</strong> Hum. Molec. Genet. 17: 3761-3766, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775957</a>] [<a href="https://doi.org/10.1093/hmg/ddn272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18775957">Sparrow et al. (2008)</a> identified homozygosity for a 73C-T transition in exon 2 of the HES7 gene, resulting in an arg25-to-trp (R25W) substitution at an evolutionarily conserved residue in the DNA-binding domain. The mutation was found in heterozygosity in the parents and 1 unaffected sib, but was not detected in 110 racially matched controls. Expression studies in mouse muscle satellite C2C12 cells using the R25W mutant in an N-box assay showed that levels of transcription were significantly increased above the control, suggesting that the R25W mutant lacks normal repression activity. In an E-box (see <a href="/entry/147141">147141</a>) assay, mutant HES7 did not repress the reporter significantly over the control, suggesting that R25W also impairs the ability of HES7 to heterodimerize with E47. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18775957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a sister and brother with spondylocostal dysostosis (SCDO4; <a href="/entry/613686">613686</a>), <a href="#9" class="mim-tip-reference" title="Sparrow, D. B., Sillence, D., Wouters, M. A., Turnpenny, P. D., Dunwoodie, S. L. <strong>Two novel missense mutations in hairy-and-enhancer-of-split-7 in a family with spondylocostal dysostosis.</strong> Europ. J. Hum. Genet. 18: 674-679, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20087400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20087400</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20087400[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2009.241" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20087400">Sparrow et al. (2010)</a> identified compound heterozygosity for a 172A-G transition in exon 3 of the HES7 gene, resulting in an ile58-to-val (I58V; <a href="#0003">608059.0003</a>) substitution, and a 556G-T transversion in exon 4, resulting in an asp186-to-tyr (D186Y) substitution. The unaffected parents were each heterozygous for 1 of the mutations, and 1 unaffected sib carried the D186Y allele; neither mutation was found in 110 ethnically matched controls. In vitro functional analysis demonstrated that the D186Y mutant was unable to repress gene expression by DNA binding or protein heterodimerization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20087400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>For discussion of the ile58-to-val (I58V) mutation in the HES7 gene that was found in compound heterozygous state in sibs with spondylocostal dysostosis-4 (SCDO4; <a href="/entry/613686">613686</a>) by <a href="#9" class="mim-tip-reference" title="Sparrow, D. B., Sillence, D., Wouters, M. A., Turnpenny, P. D., Dunwoodie, S. L. <strong>Two novel missense mutations in hairy-and-enhancer-of-split-7 in a family with spondylocostal dysostosis.</strong> Europ. J. Hum. Genet. 18: 674-679, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20087400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20087400</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20087400[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2009.241" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20087400">Sparrow et al. (2010)</a>, see <a href="#0002">608059.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20087400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs398122970 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122970;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs398122970?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs398122970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs398122970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001807779 OR RCV001854347" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001807779, RCV001854347" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001807779...</a>
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<p>In 4 patients from a large consanguineous Arab family with spondylocostal dysostosis (SCDO4; <a href="/entry/613686">613686</a>), <a href="#7" class="mim-tip-reference" title="Sparrow, D. B., Faqeih, E. A., Sallout, B., Alswaid, A., Ababneh, F., Al-Sayed, M., Rukban, H., Eyaid, W. M., Kageyama, R., Ellard, S., Turnpenny, P. D., Dunwoodie, S. L. <strong>Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus.</strong> Am. J. Med. Genet. 161A: 2244-2249, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23897666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23897666</a>] [<a href="https://doi.org/10.1002/ajmg.a.36073" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23897666">Sparrow et al. (2013)</a> identified a homozygous 10-bp duplication (c.400_409dupAAACCGCCCC) in exon 4 of the HES7 gene, predicting a frameshift and premature termination (Arg137GlnfsTer42). The same mutation was identified in 3 patients in 2 additional families from the same geographic area. Three patients also has dextrocardia with situs inversus and 2 patients also had neural tube defects. Functional analysis showed that the mutation resulted in a significant reduction in the repressive activity of HES7. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23897666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Bessho2001" class="mim-anchor"></a>
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Bessho, Y., Miyoshi, G., Sakata, R., Kageyama, R.
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<strong>Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm.</strong>
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Genes Cells 6: 175-185, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11260262/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11260262</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11260262" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1046/j.1365-2443.2001.00409.x" target="_blank">Full Text</a>]
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<a id="Diaz-Cuadros2020" class="mim-anchor"></a>
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Diaz-Cuadros, M., Wagner, D. E., Budjan, C., Hubaud, A., Tarazona, O. A., Donelly, S., Michaut, A., Al Tanoury, Z., Yoshioka-Kobayashi, K., Niino, Y., Kageyama, R., Miyawaki, A., Touboul, J., Pourguie, O.
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<strong>In vitro characterization of the human segmentation clock.</strong>
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Nature 580: 113-118, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31915384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31915384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31915384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41586-019-1885-9" target="_blank">Full Text</a>]
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<a id="Gross2013" class="mim-anchor"></a>
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 12/18/2013.
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Hirata, H., Bessho, Y., Kokubu, H., Masamizu, Y., Yamada, S., Lewis, J., Kageyama, R.
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<strong>Instability of Hes7 protein is crucial for the somite segmentation clock.</strong>
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Nature Genet. 36: 750-754, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15170214/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15170214</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15170214" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1372" target="_blank">Full Text</a>]
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Matsuda, M., Hayashi, H., Garcia-Ojalvo, J., Yoshioka-Kobayashi, K., Kageyama, R., Yamanaka, Y., Ikeya, M., Toguchida, J., Alev, C., Ebisuya, M.
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<strong>Species-specific segmentation clock periods are due to differential biochemical reaction speeds.</strong>
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Science 369: 1450-1455, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32943519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32943519</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32943519" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.aba7668" target="_blank">Full Text</a>]
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Matsuda, M., Yamanaka, Y., Uemura, M., Osawa, M., Saito, M. K., Nagahashi, A., Nishio, M., Guo, L., Ikegawa, S., Sakurai, S., Kihara, S., Maurissen, T. L., and 10 others.
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<strong>Recapitulating the human segmentation clock with pluripotent stem cells.</strong>
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Nature 580: 124-129, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32238941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32238941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32238941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41586-020-2144-9" target="_blank">Full Text</a>]
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Sparrow, D. B., Faqeih, E. A., Sallout, B., Alswaid, A., Ababneh, F., Al-Sayed, M., Rukban, H., Eyaid, W. M., Kageyama, R., Ellard, S., Turnpenny, P. D., Dunwoodie, S. L.
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<strong>Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus.</strong>
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Am. J. Med. Genet. 161A: 2244-2249, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23897666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23897666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23897666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.36073" target="_blank">Full Text</a>]
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<a id="Sparrow2008" class="mim-anchor"></a>
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Sparrow, D. B., Guillen-Navarro, E., Fatkin, D., Dunwoodie, S. L.
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<strong>Mutation of hairy-and-enhancer-of-split-7 in humans causes spondylocostal dysostosis.</strong>
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Hum. Molec. Genet. 17: 3761-3766, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18775957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18775957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18775957" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddn272" target="_blank">Full Text</a>]
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<a id="Sparrow2010" class="mim-anchor"></a>
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Sparrow, D. B., Sillence, D., Wouters, M. A., Turnpenny, P. D., Dunwoodie, S. L.
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<strong>Two novel missense mutations in hairy-and-enhancer-of-split-7 in a family with spondylocostal dysostosis.</strong>
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Europ. J. Hum. Genet. 18: 674-679, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20087400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20087400</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20087400[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20087400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2009.241" target="_blank">Full Text</a>]
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Xu, X., Sun, X., Hu, X.-S., Zhuang, Y., Liu, Y.-C., Meng, H., Miao, L., Yu, H., Luo, S.-J.
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<strong>Whole genome sequencing identifies a missense mutation in HES7 associated with short tails in Asian domestic cats.</strong>
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Sci. Rep. 6: 31583, 2016. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27560986/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27560986</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27560986[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27560986" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/srep31583" target="_blank">Full Text</a>]
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Yoshioka-Kobayashi, K., Matsumiya, M., Niino, Y., Isomura, A., Kori, H., Miyawaki, A., Kageyama, R.
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<strong>Coupling delay controls synchronized oscillation in the segmentation clock.</strong>
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Nature 580: 119-123, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31915376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31915376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31915376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41586-019-1882-z" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Ada Hamosh - updated : 03/03/2021
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Ada Hamosh - updated : 11/12/2020<br>Ada Hamosh - updated : 11/06/2020<br>Patricia A. Hartz - updated : 10/07/2016<br>Matthew B. Gross - updated : 12/18/2013<br>Sonja A. Rasmussen - updated : 12/18/2013<br>Marla J. F. O'Neill - updated : 1/10/2011<br>Victor A. McKusick - updated : 8/18/2004
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Patricia A. Hartz : 8/27/2003
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 03/03/2021
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 11/12/2020<br>mgross : 11/12/2020<br>mgross : 11/06/2020<br>carol : 01/14/2020<br>mgross : 10/07/2016<br>mgross : 10/07/2016<br>carol : 03/09/2015<br>mcolton : 2/10/2015<br>mgross : 12/18/2013<br>carol : 12/18/2013<br>carol : 12/29/2011<br>carol : 1/10/2011<br>tkritzer : 8/18/2004<br>terry : 8/18/2004<br>mgross : 8/27/2003
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<h3>
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<span class="mim-font">
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<strong>*</strong> 608059
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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HES FAMILY bHLH TRANSCRIPTION FACTOR 7; HES7
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div >
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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HAIRY/ENHANCER OF SPLIT, DROSOPHILA, HOMOLOG OF, 7
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</span>
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</h4>
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</div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: HES7</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 17p13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:8,120,592-8,126,634 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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17p13.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Spondylocostal dysostosis 4, autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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613686
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>HES7 encodes a basic helix-loop-helix-Orange domain transcriptional repressor protein that is both a direct target of the Notch signaling pathway (see 190198) and part of a negative feedback mechanism required to attenuate Notch signaling (summary by Sparrow et al., 2008) </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bessho et al. (2001) cloned mouse Hes7 and, by EST database searching and PCR, obtained a cDNA encoding human HES7. The deduced mouse and human proteins contain 225 amino acids, and both have an N-terminal basic helix-loop-helix (bHLH) domain, a central 'orange' domain, and a conserved C-terminal WRPW sequence. Human and mouse HES7 are identical in the bHLH domain and share 90.7% amino acid identity overall. Compared with other mouse HES proteins, Hes7 is most similar to Hes5 (607348), particularly in the bHLH and orange domains. Northern blot analysis of day-9.5 mouse embryos detected a 1.0-kb Hes7 transcript. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bessho et al. (2001) determined that mouse Hes7 contains 4 exons and spans about 3 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gross (2013) mapped the HES7 gene to chromosome 17p13.1 based on an alignment of the HES7 sequence (GenBank AB049064) with the genomic sequence (GRCh37).</p><p>Bessho et al. (2001) mapped the mouse Hes7 gene to chromosome 11, next to the Aloxe3 gene (607206). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By in situ hybridization of day-8.5 through day-12.0 mouse embryos, Bessho et al. (2001) found dynamic expression of Hes7 in the presomitic mesoderm (PSM). Transfection experiments determined that mouse Hes7 repressed transcription from N box- and E box-containing promoters. Hes7 also suppressed E47 (147141)-induced transcriptional activation. Promoter analysis indicated that mouse Hes7 expression was controlled by Notch signaling. </p><p>During somitogenesis, a pair of somites buds off from the PSM every 2 hours in mouse embryos, suggesting that somite segmentation is controlled by a biologic clock with a 2-hour cycle. Expression of Hes7, an effector of Notch signaling, follows a 2-hour oscillatory cycle controlled by negative feedback; it had been proposed that this is the molecular basis for the somite segmentation clock. To address the biologic importance of Hes7 instability, Hirata et al. (2004) generated mice expressing mutant Hes7 with a longer half-life but normal repressor activity. In these mice, somite segmentation and oscillatory expression became severely disorganized after a few normal cycles of segmentation. Hirata et al. (2004) simulated this effect mathematically using a direct autorepression model. Thus, instability of Hes7 is essential for sustained oscillation and for its function as a segmentation clock. </p><p>Diaz-Cuadros et al. (2020) showed that human and mouse PSM cells derived in vitro recapitulated the oscillations of the segmentation clock, as measured by expression of fluorescence-tagged HES7. Human PSM cells oscillated with a period 2 times longer than that of mouse cells (5 vs 2.5 hours, respectively), but were similarly regulated by FGF (see 131220), Wnt (see 606359), Notch, and YAP (YAP1; 606608) signaling. Single-cell RNA sequencing revealed that mouse and human PSM cells in vitro followed a developmental trajectory similar to that of mouse PSM cells in vivo. Furthermore, Diaz-Cuadros et al. (2020) demonstrated that FGF signaling controlled the phase and period of oscillations, expanding the role of this pathway beyond its classical interpretation in 'clock and wavefront' models. </p><p>Yoshioka-Kobayashi et al. (2020) established a live-imaging system in which a fluorescent reporter was fused to Hes7 to monitor synchronous oscillations in Hes7 expression in mouse PSM at single-cell resolution. They found that wildtype PSM cells could rapidly correct for phase fluctuations in Hes7 oscillations, whereas loss of the Notch modulator Lfng (602576) led to loss of synchrony between PSM cells. Moreover, Hes7 oscillations were severely dampened in individual cells of Lfng-null PSM. When Lfng-null PSM cells were completely dissociated, the amplitude and periodicity of Hes7 oscillations were almost normal, suggesting that Lfng is involved mostly in cell-cell coupling. Mixed cultures of wildtype and Lfng-null PSM cells, and an optogenetic Notch signaling reporter assay, revealed that Lfng delayed the signal-sending process of intercellular Notch signaling transmission. These results, as well as mathematical modeling, suggested that Lfng-null PSM cells shortened the coupling delay, thereby approaching oscillation or amplitude death of coupled oscillators. A small compound that lengthened the coupling delay partially rescued the amplitude and synchrony of Hes7 oscillations in Lfng-null PSM cells. The findings revealed a delay control mechanism of the oscillatory networks involved in somite segmentation and showed that intercellular coupling with the correct delay is essential for synchronized oscillation. </p><p>Matsuda et al. (2020) used human induced pluripotent stem cells for in vitro induction of PSM and its derivatives to model human somitogenesis, with a focus on the human segmentation clock. The authors observed oscillatory expression of core segmentation clock genes, including HES7 and DKK1 (605189), determined the period of the human segmentation clock to be around 5 hours, and demonstrated the presence of dynamic traveling wave-like gene expression in in vitro-induced human PSM. Identification and comparison of oscillatory genes in human and mouse PSM derived from pluripotent stem cells revealed species-specific and shared molecular components and pathways associated with the putative mouse and human segmentation clocks. Knockout of genes mutated in patients with segmentation defects of vertebrae, including HES7, LFNG, DLL3 (602768), and MESP2 (605195), followed by analysis of patient-like and patient-derived induced pluripotent stem cells revealed gene-specific alterations in oscillation, synchronization, or differentiation properties. </p><p>To investigate interspecies differences in the time scale of development, Matsuda et al. (2020) recapitulated murine and human segmentation clocks displaying 2- to 3-hour and 5- to 6-hour oscillation periods, respectively. Interspecies genome-swapping analyses showed that the period difference was not due to sequence differences in HES7. Instead, multiple biochemical reactions of HES7, including degradation and expression delays, were slower in human cells than in mouse cells. With the measured biochemical parameters, the authors built a mathematical model accounting for the 2- to 3-fold period difference between the species. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In the proband of a consanguineous family of Caucasian Mediterranean origin with spondylocostal dysostosis mapping to chromosome 17p13 (SCDO4; 613686), Sparrow et al. (2008) identified homozygosity for a missense mutation in the HES7 gene (R25W; 608059.0001). </p><p>In a brother and sister with SCDO from a nonconsanguineous Italian family, Sparrow et al. (2010) sequenced the 4 genes known to cause SCDO and identified compound heterozygosity for missense mutations in the HES7 gene (608059.0002 and 608059.0003). </p><p>In 7 patients from 3 families with SCDO, Sparrow et al. (2013) identified a homozygous frameshift mutation in the HES7 gene (608059.0004) that resulted in significant reduction of HES7 protein function. Four patients were from a consanguineous Arab family and the other patients were from 2 additional families from the same geographic area. Three patients also had dextrocardia with situs inversus and 2 patients also had neural tube defects. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Cats with variably shortened and/or kinked tails are widespread in Southeast Asia and southern China. Xu et al. (2016) established a 2-generation pedigree of 13 cats in which the dam appeared to be heterozygous for a tail with medium kink and the sire was wildtype. Radiography revealed that wildtype cats had 22 caudal vertebrae with no sign of deformity, whereas the kinked-tail dam and affected offspring exhibited reduced number of vertebrae and variable deformity, including hemivertebrae and block caudal vertebrae. Linkage analysis and whole-genome sequencing revealed that tail shortening and kinking was due to a c.5T-C transition in Hes7, resulting in a val2-to-ala (V2A) substitution. Val2 lies upstream of the bHLH domain and is completely conserved in vertebrates. In an extended sampling of 245 unrelated cats, the authors found that a significant number with shortened and/or kinked tails carried the Hes7 mutation. The results suggested that V2A is strongly associated with short/kinked tail with a dominant mode of inheritance. Cats homozygous for the V2A mutation showed tails with extreme kink, whereas heterozygotes had either minor or medium kink, suggesting a dose effect of V2A on tail morphology. No wildtype cats carried the mutation. Other than the tail abnormality, feral cats heterozygous or homozygous for V2A appeared normal and had no apparent health hazards. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>4 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 SPONDYLOCOSTAL DYSOSTOSIS 4</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HES7, ARG25TRP
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<br />
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SNP: rs113994160,
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ClinVar: RCV000034271, RCV002269820
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In the proband of a consanguineous family of Caucasian Mediterranean origin with spondylocostal dysostosis (SCDO4; 613686), Sparrow et al. (2008) identified homozygosity for a 73C-T transition in exon 2 of the HES7 gene, resulting in an arg25-to-trp (R25W) substitution at an evolutionarily conserved residue in the DNA-binding domain. The mutation was found in heterozygosity in the parents and 1 unaffected sib, but was not detected in 110 racially matched controls. Expression studies in mouse muscle satellite C2C12 cells using the R25W mutant in an N-box assay showed that levels of transcription were significantly increased above the control, suggesting that the R25W mutant lacks normal repression activity. In an E-box (see 147141) assay, mutant HES7 did not repress the reporter significantly over the control, suggesting that R25W also impairs the ability of HES7 to heterodimerize with E47. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 SPONDYLOCOSTAL DYSOSTOSIS 4</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HES7, ASP186TYR
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<br />
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SNP: rs387906978,
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gnomAD: rs387906978,
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ClinVar: RCV001807738
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a sister and brother with spondylocostal dysostosis (SCDO4; 613686), Sparrow et al. (2010) identified compound heterozygosity for a 172A-G transition in exon 3 of the HES7 gene, resulting in an ile58-to-val (I58V; 608059.0003) substitution, and a 556G-T transversion in exon 4, resulting in an asp186-to-tyr (D186Y) substitution. The unaffected parents were each heterozygous for 1 of the mutations, and 1 unaffected sib carried the D186Y allele; neither mutation was found in 110 ethnically matched controls. In vitro functional analysis demonstrated that the D186Y mutant was unable to repress gene expression by DNA binding or protein heterodimerization. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 SPONDYLOCOSTAL DYSOSTOSIS 4</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HES7, ILE58VAL
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<br />
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SNP: rs387906979,
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ClinVar: RCV001807739
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the ile58-to-val (I58V) mutation in the HES7 gene that was found in compound heterozygous state in sibs with spondylocostal dysostosis-4 (SCDO4; 613686) by Sparrow et al. (2010), see 608059.0002. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<span class="mim-font">
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<strong>.0004 SPONDYLOCOSTAL DYSOSTOSIS 4</strong>
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</h4>
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<span class="mim-text-font">
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HES7, 10-BP DUP, NT400
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<br />
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SNP: rs398122970,
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gnomAD: rs398122970,
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ClinVar: RCV001807779, RCV001854347
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<p>In 4 patients from a large consanguineous Arab family with spondylocostal dysostosis (SCDO4; 613686), Sparrow et al. (2013) identified a homozygous 10-bp duplication (c.400_409dupAAACCGCCCC) in exon 4 of the HES7 gene, predicting a frameshift and premature termination (Arg137GlnfsTer42). The same mutation was identified in 3 patients in 2 additional families from the same geographic area. Three patients also has dextrocardia with situs inversus and 2 patients also had neural tube defects. Functional analysis showed that the mutation resulted in a significant reduction in the repressive activity of HES7. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Bessho, Y., Miyoshi, G., Sakata, R., Kageyama, R.
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<strong>Hes7: a bHLH-type repressor gene regulated by Notch and expressed in the presomitic mesoderm.</strong>
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Genes Cells 6: 175-185, 2001.
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[PubMed: 11260262]
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[Full Text: https://doi.org/10.1046/j.1365-2443.2001.00409.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Diaz-Cuadros, M., Wagner, D. E., Budjan, C., Hubaud, A., Tarazona, O. A., Donelly, S., Michaut, A., Al Tanoury, Z., Yoshioka-Kobayashi, K., Niino, Y., Kageyama, R., Miyawaki, A., Touboul, J., Pourguie, O.
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<strong>In vitro characterization of the human segmentation clock.</strong>
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Nature 580: 113-118, 2020.
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[PubMed: 31915384]
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[Full Text: https://doi.org/10.1038/s41586-019-1885-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 12/18/2013.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hirata, H., Bessho, Y., Kokubu, H., Masamizu, Y., Yamada, S., Lewis, J., Kageyama, R.
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<strong>Instability of Hes7 protein is crucial for the somite segmentation clock.</strong>
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Nature Genet. 36: 750-754, 2004.
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[PubMed: 15170214]
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[Full Text: https://doi.org/10.1038/ng1372]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Matsuda, M., Hayashi, H., Garcia-Ojalvo, J., Yoshioka-Kobayashi, K., Kageyama, R., Yamanaka, Y., Ikeya, M., Toguchida, J., Alev, C., Ebisuya, M.
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<strong>Species-specific segmentation clock periods are due to differential biochemical reaction speeds.</strong>
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Science 369: 1450-1455, 2020.
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[PubMed: 32943519]
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[Full Text: https://doi.org/10.1126/science.aba7668]
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</li>
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<li>
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<p class="mim-text-font">
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Matsuda, M., Yamanaka, Y., Uemura, M., Osawa, M., Saito, M. K., Nagahashi, A., Nishio, M., Guo, L., Ikegawa, S., Sakurai, S., Kihara, S., Maurissen, T. L., and 10 others.
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<strong>Recapitulating the human segmentation clock with pluripotent stem cells.</strong>
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Nature 580: 124-129, 2020.
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[PubMed: 32238941]
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[Full Text: https://doi.org/10.1038/s41586-020-2144-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Sparrow, D. B., Faqeih, E. A., Sallout, B., Alswaid, A., Ababneh, F., Al-Sayed, M., Rukban, H., Eyaid, W. M., Kageyama, R., Ellard, S., Turnpenny, P. D., Dunwoodie, S. L.
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<strong>Mutation of HES7 in a large extended family with spondylocostal dysostosis and dextrocardia with situs inversus.</strong>
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Am. J. Med. Genet. 161A: 2244-2249, 2013.
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[PubMed: 23897666]
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[Full Text: https://doi.org/10.1002/ajmg.a.36073]
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</p>
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<li>
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<p class="mim-text-font">
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Sparrow, D. B., Guillen-Navarro, E., Fatkin, D., Dunwoodie, S. L.
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<strong>Mutation of hairy-and-enhancer-of-split-7 in humans causes spondylocostal dysostosis.</strong>
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Hum. Molec. Genet. 17: 3761-3766, 2008.
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[PubMed: 18775957]
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[Full Text: https://doi.org/10.1093/hmg/ddn272]
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</p>
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<li>
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<p class="mim-text-font">
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Sparrow, D. B., Sillence, D., Wouters, M. A., Turnpenny, P. D., Dunwoodie, S. L.
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<strong>Two novel missense mutations in hairy-and-enhancer-of-split-7 in a family with spondylocostal dysostosis.</strong>
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Europ. J. Hum. Genet. 18: 674-679, 2010.
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[PubMed: 20087400]
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[Full Text: https://doi.org/10.1038/ejhg.2009.241]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Xu, X., Sun, X., Hu, X.-S., Zhuang, Y., Liu, Y.-C., Meng, H., Miao, L., Yu, H., Luo, S.-J.
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<strong>Whole genome sequencing identifies a missense mutation in HES7 associated with short tails in Asian domestic cats.</strong>
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Sci. Rep. 6: 31583, 2016. Note: Electronic Article.
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[PubMed: 27560986]
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[Full Text: https://doi.org/10.1038/srep31583]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Yoshioka-Kobayashi, K., Matsumiya, M., Niino, Y., Isomura, A., Kori, H., Miyawaki, A., Kageyama, R.
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<strong>Coupling delay controls synchronized oscillation in the segmentation clock.</strong>
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Nature 580: 119-123, 2020.
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[PubMed: 31915376]
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[Full Text: https://doi.org/10.1038/s41586-019-1882-z]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 03/03/2021<br>Ada Hamosh - updated : 11/12/2020<br>Ada Hamosh - updated : 11/06/2020<br>Patricia A. Hartz - updated : 10/07/2016<br>Matthew B. Gross - updated : 12/18/2013<br>Sonja A. Rasmussen - updated : 12/18/2013<br>Marla J. F. O'Neill - updated : 1/10/2011<br>Victor A. McKusick - updated : 8/18/2004
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Patricia A. Hartz : 8/27/2003
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mgross : 03/03/2021<br>mgross : 11/12/2020<br>mgross : 11/12/2020<br>mgross : 11/06/2020<br>carol : 01/14/2020<br>mgross : 10/07/2016<br>mgross : 10/07/2016<br>carol : 03/09/2015<br>mcolton : 2/10/2015<br>mgross : 12/18/2013<br>carol : 12/18/2013<br>carol : 12/29/2011<br>carol : 1/10/2011<br>tkritzer : 8/18/2004<br>terry : 8/18/2004<br>mgross : 8/27/2003
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