3519 lines
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Entry
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- *182279 - SMALL NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE N; SNRPN
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- OMIM
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<p>
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<span class="h4">*182279</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<a href="#title"><strong>Title</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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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cytogenetics">Cytogenetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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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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<li role="presentation">
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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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</ul>
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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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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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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 id="mimExternalLinksFold" class="collapse in">
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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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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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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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</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=ENSG00000128739;t=ENST00000390687" 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=6638" 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=182279" 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="mimDna">
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<span class="panel-title">
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<span class="small">
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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=ENSG00000128739;t=ENST00000390687" 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_001349454,NM_001349455,NM_001349456,NM_001349457,NM_001349458,NM_001349459,NM_001349460,NM_001349461,NM_001349462,NM_001349463,NM_001349464,NM_001349465,NM_001378249,NM_001378251,NM_001378252,NM_001378253,NM_001378254,NM_001378255,NM_001378256,NM_001378257,NM_001400634,NM_001400635,NM_001400636,NM_001400637,NM_001400638,NM_001400639,NM_001400640,NM_001400641,NM_001400643,NM_001400644,NM_001400646,NM_001400647,NM_001400649,NM_001400650,NM_001400652,NM_001400683,NM_001400684,NM_001400685,NM_001400686,NM_001400687,NM_001400688,NM_001400689,NM_001400690,NM_001400691,NM_001400692,NM_001400693,NM_001400694,NM_001400695,NM_001400696,NM_001400697,NM_001400698,NM_001400701,NM_001400702,NM_001400703,NM_001400704,NM_001400706,NM_001400708,NM_001400710,NM_001400712,NM_001400713,NM_001400715,NM_001400716,NM_001400717,NM_001400718,NM_001400719,NM_001400720,NM_001400721,NM_001400722,NM_001400723,NM_001400724,NM_001400725,NM_001400726,NM_001400727,NM_001400728,NM_001400729,NM_001400730,NM_001400731,NM_001400732,NM_001400733,NM_001400734,NM_001400735,NM_001400736,NM_001400737,NM_001400738,NM_001400739,NM_001400740,NM_001400741,NM_001400742,NM_001400743,NM_001400744,NM_001400745,NM_001400746,NM_001400747,NM_001400748,NM_001400753,NM_001400754,NM_001400755,NM_001400756,NM_001400757,NM_001400758,NM_001400759,NM_001400762,NM_001400763,NM_001400764,NM_001400765,NM_001400767,NM_001400768,NM_003097,NM_022805,NM_022806,NM_022807,NM_022808" 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_003097" 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=182279" 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=01653&isoform_id=01653_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/SNRPN" 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/32040,36495,338247,1145775,4507135,5870123,12653657,13027644,13027646,13027648,13027650,13112013,15217059,19264004,22137346,47496647,52783794,62896825,119578017,119578018,119578019,119578020,119578021,119578022,119578023,119578024,119578025,119578026,119578027,193784720,608785499,1160351423,1160351430,1160351434,1160351441,1160351443,1160351445,1160351450,1160351463,1160351469,1160351471,1160351480,1160351482,1805791138,1805791152,1805791159,1805791163,1805791187,1806142213,1806142246,1806142250,2183705632,2183705635,2183705731,2183705742,2183705748,2183705754,2183705757,2183705759,2183705761,2183705763,2183705765,2183705767,2183705773,2183705778,2183705780,2183705782,2183705798,2183705800,2183705802,2183705883,2183705904,2183705929,2183706050,2183706083,2183706100,2183706145,2183706163,2183706168,2183706182,2183706199,2183706286,2183706342,2183706392,2183706419,2183706461,2183706463,2183706465,2183706469,2183706479,2183706481,2183706489,2183706491,2183706495,2183706499,2183706501,2183706507,2183706509,2183706513,2183706526,2183706566,2183706604,2183706607,2183706609,2183706647,2183706749,2183706819,2183706831,2183706833,2183706835,2183706837,2183706840,2183706842,2183706847,2183706851,2183706861,2183706863,2183706865,2183706867,2183706869,2183706935,2183706960,2183707116,2183707125,2183707131,2183707148,2183707161,2183707167,2183707169,2183707183,2183707185,2183707191,2183707193,2183707243,2183707260,2183707409,2183707413,2183707421" 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/P63162" 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=6638" 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=ENSG00000128739;t=ENST00000390687" 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=SNRPN" 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=SNRPN" 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+6638" 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/SNRPN" 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:6638" 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/6638" 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>
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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://search.clinicalgenome.org/kb/gene-dosage/HGNC:11164" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=182279[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>
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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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<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=182279[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/ENSG00000128739" 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=SNRPN" 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=SNRPN" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SNRPN&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/PA36005" 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 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:11164" 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://flybase.org/reports/FBgn0262601.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:98347" 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/SNRPN#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:98347" 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/6638/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://www.orthodb.org/?ncbi=6638" 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://wormbase.org/db/gene/gene?name=WBGene00004915;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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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="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:182279" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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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://reactome.org/content/query?q=SNRPN&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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<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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<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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182279
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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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SMALL NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE N; SNRPN
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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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SMN
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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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<a id="includedTitles" 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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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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SNRPN UPSTREAM READING FRAME, INCLUDED; SNURF, INCLUDED
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</span>
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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=SNRPN" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SNRPN</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/15/26?start=-3&limit=10&highlight=26">15q11.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:24823637-24978723&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">15:24,823,637-24,978,723</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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</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.">
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<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>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<p>SNRPN, or SNURF-SNRPN, is a bicistronic imprinted gene that encodes 2 polypeptides, the SmN splicing factor, which is involved in RNA processing, and the SNRPN upstream reading frame (SNURF) polypeptide. The SNRPN gene is transcribed exclusively from the paternally inherited chromosome and shows highest expression in brain and heart. SNRPN is located within an imprinted gene cluster in chromosome 15 that is associated with Prader-Willi syndrome (PWS; <a href="/entry/176270">176270</a>) and Angelman syndrome (AS; <a href="/entry/105830">105830</a>), 2 clinically distinct neurogenetic disorders. PWS arises from loss of function of genes in this region expressed exclusively from the paternal chromosome, suggesting that SNRPN may play a role in its etiology (<a href="#24" class="mim-tip-reference" title="Rodriguez-Jato, S., Nicholls, R. D, Driscoll, D. J., Yang, T. P. <strong>Characterization of cis- and trans-acting elements in the imprinted human SNURF-SNRPN locus.</strong> Nucleic Acids Res. 33: 4740-4753, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116039/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116039</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16116039[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/10.1093/nar/gki786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116039">Rodriguez-Jato et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116039" 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>Small nuclear ribonucleoprotein particles (snRNP) found in spliceosomes contain small RNAs U1 (<a href="/entry/180680">180680</a>), U2 (<a href="/entry/180690">180690</a>), U4, U5 (<a href="/entry/180691">180691</a>), and U6 (<a href="/entry/180692">180692</a>), and associated polypeptides. Some of these polypeptides are present in all 5 of these snRNPs and others are unique to U1 or U2 snRNPs or have tissue-limited expression patterns. SnRNP-associated proteins have epitopes that react with autoimmune sera. With such an antiserum (Sm), a protein termed SmN was identified and the gene subsequently cloned (<a href="#19" class="mim-tip-reference" title="McAllister, G., Amara, S. G., Lerner, M. R. <strong>Tissue-specific expression and cDNA cloning of small nuclear ribonucleoprotein-associated polypeptide N.</strong> Proc. Nat. Acad. Sci. 85: 5296-5300, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2969109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2969109</a>] [<a href="https://doi.org/10.1073/pnas.85.14.5296" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2969109">McAllister et al., 1988</a>; <a href="#14" class="mim-tip-reference" title="Li, S., Klein, E. S., Russo, A. F., Simmons, D. M., Rosenfeld, M. G. <strong>Isolation of cDNA clones encoding small nuclear ribonucleoparticle-associated proteins with different tissue specificities.</strong> Proc. Nat. Acad. Sci. 86: 9778-9782, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2532363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2532363</a>] [<a href="https://doi.org/10.1073/pnas.86.24.9778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2532363">Li et al., 1989</a>; <a href="#27" class="mim-tip-reference" title="Schmauss, C., McAllister, G., Ohosone, Y., Hardin, J. A., Lerner, M. R. <strong>A comparison of snRNP-associated Sm-autoantigens: human N, rat N and human B/B-prime.</strong> Nucleic Acids Res. 17: 1733-1743, 1989. Note: Erratum: Nucleic Acids Res. 17: 6777 only, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2522186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2522186</a>] [<a href="https://doi.org/10.1093/nar/17.4.1733" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2522186">Schmauss et al., 1989</a>). Although the sequence of SmN shows it to be highly homologous to the ubiquitous core snRNP protein B and its alternatively spliced form B-prime, <a href="#21" class="mim-tip-reference" title="Ozcelik, T., Leff, S., Robinson, W., Donlon, T., Lalande, M., Sanjines, E., Schinzel, A., Francke, U. <strong>Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region.</strong> Nature Genet. 2: 265-269, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303277</a>] [<a href="https://doi.org/10.1038/ng1292-265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303277">Ozcelik et al. (1992)</a> noted that SmN is expressed predominantly in brain and especially in central neurons. They suggested that SmN may be involved in brain-specific mRNA splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2969109+2522186+2532363+1303277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>SNRPN Upstream Reading Frame (SNURF)</em></strong></p><p>
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<a href="#31" class="mim-tip-reference" title="Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G. <strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong> Hum. Molec. Genet. 5: 517-524, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845846</a>] [<a href="https://doi.org/10.1093/hmg/5.4.517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845846">Sun et al. (1996)</a> reported a patient with PWS phenotype and a balanced reciprocal translocation t(15;19)(q12;q13.41) of paternal origin in which the breakpoint occurred between exons 0 and 1 of the SNRPN locus, outside of the SmN open reading frame. Based on their findings, <a href="#31" class="mim-tip-reference" title="Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G. <strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong> Hum. Molec. Genet. 5: 517-524, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845846</a>] [<a href="https://doi.org/10.1093/hmg/5.4.517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845846">Sun et al. (1996)</a> suggested that the 3 upstream exons (exons -1, 0, and 1) of SNRPN encode an additional independent reading frame, SNURF (SNRPN upstream reading frame). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845846" 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>Polycistronic transcripts are common in prokaryotes but rare in eukaryotes. <a href="#9" class="mim-tip-reference" title="Gray, T. A., Saitoh, S., Nicholls, R. D. <strong>An imprinted, mammalian bicistronic transcript encodes two independent proteins.</strong> Proc. Nat. Acad. Sci. 96: 5616-5621, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10318933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10318933</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10318933[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.10.5616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10318933">Gray et al. (1999)</a> found that 5 eutherian mammals (cow, rat, mouse, rabbit, and human) have the highly conserved SNURF coding sequence. The vast majority of nucleotide substitutions in SNURF were found to be in the wobble codon position, providing strong evolutionary evidence for selection for protein-coding function. Because SNURF-SNRPN maps to human chromosome 15q11-q13 and is paternally expressed, each cistron is a candidate for a role in the imprinted PWS and PWS mouse models. SNURF encodes a highly basic 71-amino acid protein that is nuclear-localized (as is the product of the SNRPN gene). Because SNURF is the only protein-coding sequence within the imprinting regulatory region in 15q11-q13, it may have provided the original selection for imprinting in this domain. Whereas some human tissues express a minor SNURF-only transcript, mouse tissues express only the bicistronic Snurf-Snrpn transcript. <a href="#9" class="mim-tip-reference" title="Gray, T. A., Saitoh, S., Nicholls, R. D. <strong>An imprinted, mammalian bicistronic transcript encodes two independent proteins.</strong> Proc. Nat. Acad. Sci. 96: 5616-5621, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10318933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10318933</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10318933[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.96.10.5616" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10318933">Gray et al. (1999)</a> showed that both SNURF and SNRPN are translated in normal, but not PWS, human and mouse tissues and cell lines. These findings identified SNURF as a protein that is produced along with SNRPN from a bicistronic transcript; polycistronic mRNAs, therefore, are encoded in mammalian genomes where they may form functional operons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10318933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By database analysis, <a href="#34" class="mim-tip-reference" title="Wawrzik, M., Spiess, A.-N., Herrmann, R., Buiting, K., Horsthemke, B. <strong>Expression of SNURF-SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis.</strong> Europ. J. Hum. Genet. 17: 1463-1470, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19471314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19471314</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19471314[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.2009.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19471314">Wawrzik et al. (2009)</a> identified several novel transcripts from the SNURF-SNRPN region, 1 of which included exon 23 from the upstream PWRN1 gene (<a href="/entry/611215">611215</a>). Exon connection PCR analysis of fetal brain and testis detected 4 transcripts, including 2 that showed splicing between a 3-prime PWRN1 exon and SNURF-SNRPN exons. <a href="#34" class="mim-tip-reference" title="Wawrzik, M., Spiess, A.-N., Herrmann, R., Buiting, K., Horsthemke, B. <strong>Expression of SNURF-SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis.</strong> Europ. J. Hum. Genet. 17: 1463-1470, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19471314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19471314</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19471314[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.2009.83" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19471314">Wawrzik et al. (2009)</a> suggested that PWNR1 is not an independent gene, but an alternative 5-prime part of SNURF-SNRPN. They also identified a transcript of unknown identity from this region, represented in GenBank as <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC035402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC035402</a>, that was upregulated in testis at meiosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19471314" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>UBE3A Antisense Transcript</em></strong></p><p>
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<a href="#25" class="mim-tip-reference" title="Runte, M., Huttenhofer, A., Gross, S., Kiefmann, M., Horsthemke, B., Buiting, K. <strong>The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A.</strong> Hum. Molec. Genet. 10: 2687-2700, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11726556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11726556</a>] [<a href="https://doi.org/10.1093/hmg/10.23.2687" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11726556">Runte et al. (2001)</a> reported that a long processed antisense transcript of UBE3A (<a href="/entry/601623">601623</a>) starts at the imprinting center (IC) at the 5-prime end of the SNURF-SNRPN gene. For further information on this antisense transcript, see SNHG14 (<a href="/entry/616259">616259</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11726556" 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="#25" class="mim-tip-reference" title="Runte, M., Huttenhofer, A., Gross, S., Kiefmann, M., Horsthemke, B., Buiting, K. <strong>The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A.</strong> Hum. Molec. Genet. 10: 2687-2700, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11726556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11726556</a>] [<a href="https://doi.org/10.1093/hmg/10.23.2687" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11726556">Runte et al. (2001)</a> determined that the SNURF-SNRPN core gene has 10 exons. Exons 1 through 3 encode SNURF, and exons 4 through 10 encode SNRPN. Upstream exon U5 includes the AS-IC element, whereas exon 1 includes the PWS-IC element. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11726556" 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>For further information on the transcriptional unit that includes SNURF-SNRPN, see SNHG14 (<a href="/entry/616259">616259</a>).</p>
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<p>By study of somatic cell hybrids and hybrid cell lines, <a href="#21" class="mim-tip-reference" title="Ozcelik, T., Leff, S., Robinson, W., Donlon, T., Lalande, M., Sanjines, E., Schinzel, A., Francke, U. <strong>Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region.</strong> Nature Genet. 2: 265-269, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303277</a>] [<a href="https://doi.org/10.1038/ng1292-265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303277">Ozcelik et al. (1992)</a> mapped the SNRPN gene to chromosome 15q12 and a processed pseudogene, SNRPNP1, to chromosome 6pter-p21. Furthermore, they showed that SNRPN maps to the minimal deletion interval that is critical for Prader-Willi syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Mutirangura, A., Jayakumar, A., Sutcliffe, J. S., Nakao, M., McKinney, M. J., Buiting, K., Horsthemke, B., Beaudet, A. L., Chinault, A. C., Ledbetter, D. H. <strong>A complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13) and refined localization of the SNRPN gene.</strong> Genomics 18: 546-552, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8307564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8307564</a>] [<a href="https://doi.org/10.1016/s0888-7543(11)80011-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8307564">Mutirangura et al. (1993)</a> constructed a complete YAC contig of the Prader-Willi/Angelman syndrome chromosome region and localized the SNRPN gene to specific YACs within the contig. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8307564" 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="#13" class="mim-tip-reference" title="Leff, S. E., Brannan, C. I., Reed, M. L., Ozcelik, T., Francke, U., Copeland, N. G., Jenkins, N. A. <strong>Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region.</strong> Nature Genet. 2: 259-264, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303276</a>] [<a href="https://doi.org/10.1038/ng1292-259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303276">Leff et al. (1992)</a> showed that the mouse Snrpn gene maps to chromosome 7 in a region of homology with human chromosome 15q11-q13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303276" 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><strong><em>Imprinting of SNRPN</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Leff, S. E., Brannan, C. I., Reed, M. L., Ozcelik, T., Francke, U., Copeland, N. G., Jenkins, N. A. <strong>Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region.</strong> Nature Genet. 2: 259-264, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303276/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303276</a>] [<a href="https://doi.org/10.1038/ng1292-259" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303276">Leff et al. (1992)</a> demonstrated that the Snrpn gene is maternally imprinted in the mouse, suggesting that loss of the paternally derived SNRPN allele may be involved in the PWS phenotype. <a href="#4" class="mim-tip-reference" title="Cattanach, B. M., Barr, J. A., Evans, E. P., Burtenshaw, M., Beechey, C. V., Leff, S. E., Brannan, C. I., Copeland, N. G., Jenkins, N. A., Jones, J. <strong>A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression.</strong> Nature Genet. 2: 270-274, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303278</a>] [<a href="https://doi.org/10.1038/ng1292-270" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1303278">Cattanach et al. (1992)</a> reported observations indicating that maternal duplication of the central part of mouse chromosome 7, where the Snrpn gene is located, causes an imprinting effect that may correspond to PWS. Paternal duplication was not associated with any detectable effect that might correspond with Angelman syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1303276+1303278" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Glenn, C. C., Porter, K. A., Jong, M. T. C., Nicholls, R. D., Driscoll, D. J. <strong>Functional imprinting and epigenetic modification of the human SNRPN gene.</strong> Hum. Molec. Genet. 2: 2001-2005, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111367</a>] [<a href="https://doi.org/10.1093/hmg/2.12.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8111367">Glenn et al. (1993)</a> demonstrated functional imprinting of the human SNRPN gene using RT-PCR. No expression was observed in cultured skin fibroblasts of patients with Prader-Willi syndrome but was found in all patients with Angelman syndrome and in normal controls. <a href="#8" class="mim-tip-reference" title="Glenn, C. C., Porter, K. A., Jong, M. T. C., Nicholls, R. D., Driscoll, D. J. <strong>Functional imprinting and epigenetic modification of the human SNRPN gene.</strong> Hum. Molec. Genet. 2: 2001-2005, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8111367/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8111367</a>] [<a href="https://doi.org/10.1093/hmg/2.12.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8111367">Glenn et al. (1993)</a> also demonstrated a parent-specific DNA methylation imprint within intron 5 of the SNRPN gene, which suggested an epigenetic mechanism by which parent-specific expression of this gene might be inherited. Thus, the authors found that the pattern of imprinting fulfills 1 major criterion for SNRPN being involved in pathogenesis of PWS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8111367" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Reed, M. L., Leff, S. E. <strong>Maternal imprinting of human SNRPN, a gene deleted in Prader-Willi syndrome.</strong> Nature Genet. 6: 163-167, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7512861/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7512861</a>] [<a href="https://doi.org/10.1038/ng0294-163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7512861">Reed and Leff (1994)</a> characterized a sequence polymorphism within expressed portions of the human SNRPN gene and showed that the SNRPN gene is monoallelically expressed in fetal brain and heart and in adult brain. Analysis of maternal DNA and of SNRPN cDNA confirmed that the maternal allele is not expressed in fetal brain and heart. Thus, maternal imprinting of SNRPN supports the hypothesis that paternal absence of SNRPN is responsible for the PWS phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7512861" 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 examine the chromatin basis of imprinting in the 15q11-q13 region, <a href="#26" class="mim-tip-reference" title="Saitoh, S., Wada, T. <strong>Parent-of-origin specific histone acetylation and reactivation of a key imprinted gene locus in Prader-Willi syndrome.</strong> Am. J. Hum. Genet. 66: 1958-1962, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10775525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10775525</a>] [<a href="https://doi.org/10.1086/302917" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10775525">Saitoh and Wada (2000)</a> investigated the status of histone acetylation of the SNURF-SNRPN locus, which is a key imprinted gene in PWS. Chromatin immunoprecipitation studies showed that the unmethylated CpG island of the active, paternally derived allele associated with acetylated histones, whereas the methylated maternally derived, inactive allele was specifically hypoacetylated. The body of the SNURF-SNRPN gene was associated with acetylated histones on both alleles. Treatment of PWS cells with the DNA methyltransferase inhibitor 5-azadeoxycytidine induced demethylation of the SNURF-SNRPN CpG island and restored gene expression on the maternal allele. The reactivation was associated with increased H4 acetylation but not with H3 acetylation at the SNURF-SNRPN CpG island. These findings indicated that (1) a significant role for histone deacetylation in gene silencing is associated with imprinting in 15q11-q13, and (2) silenced genes in PWS can be reactivated by drug treatment. Thus, the potential for pharmaceutical treatment of imprinting-related disorders was raised. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10775525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Zfp57 (<a href="/entry/612192">612192</a>) mutant mice, <a href="#15" class="mim-tip-reference" title="Li, X., Ito, M., Zhou, F., Youngson, N., Zuo, X., Leder, P., Ferguson-Smith, A. C. <strong>A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints.</strong> Dev. Cell 15: 547-557, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18854139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18854139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18854139[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.devcel.2008.08.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18854139">Li et al. (2008)</a> found that Zfp57 was required for maternal imprinting at the Snrpn locus in the female germline. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18854139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>SNRPN-Associated Imprinting Center</em></strong></p><p>
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<a href="#5" class="mim-tip-reference" title="Dittrich, B., Buiting, K., Korn, B., Rickard, S., Buxton, J., Saitoh, S., Nicholls, R. D., Poustka, A., Winterpacht, A., Zabel, B., Horsthemke, B. <strong>Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene.</strong> Nature Genet. 14: 163-170, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841186</a>] [<a href="https://doi.org/10.1038/ng1096-163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841186">Dittrich et al. (1996)</a> reported the existence of an imprinting center, which maps to a 100-kb region of chromosome 15q11-q13. This imprinting center encodes alternative transcripts of the SNRPN gene. The novel exons lack protein coding potential and are expressed from the paternal chromosome only. They also reported that families with imprinting mutations have mutations in this transcription unit. Deletions and point mutations of the alternative 5-prime exons of SNRPN (referred to as BD transcripts) are associated with a block of the maternal-paternal imprint switch in several families with Angelman syndrome. Deletions of SNRPN exon 1 are associated with a block of the maternal-paternal imprint switch in several families with Prader-Willi syndrome. Based on their studies, <a href="#5" class="mim-tip-reference" title="Dittrich, B., Buiting, K., Korn, B., Rickard, S., Buxton, J., Saitoh, S., Nicholls, R. D., Poustka, A., Winterpacht, A., Zabel, B., Horsthemke, B. <strong>Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene.</strong> Nature Genet. 14: 163-170, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841186</a>] [<a href="https://doi.org/10.1038/ng1096-163" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8841186">Dittrich et al. (1996)</a> proposed a model for imprint switching. In this model the imprint center consists of an imprinter and an imprint switch initiation site. The imprinter encodes the BD transcript. They proposed that the imprinter is transcribed from the paternal chromosome only and that it acts in cis on the switch initiation site (the SNRPN promoter, exon 1, or a site close by), possibly by introducing a change in chromatin structure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841186" 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>Prader-Willi syndrome and Angelman syndrome are neurogenetic disorders caused by the lack of a paternal or a maternal contribution from human 15q11-q13, respectively. They involve oppositely imprinted genes: the paternally expressed PWS gene(s) and the maternally expressed AS gene. Deletions in the transcription unit of the imprinted SNRPN gene occur in patients who have PWS or Angelman syndrome because of a parental imprint switch failure in this chromosomal domain. It has been suggested that the SNRPN exon 1 region, which is deleted in PWS patients, contains an imprint switch element from which the maternal and paternal epigenotypes of the 15q11-q13 domain originate. Using the model organism Drosophila, <a href="#16" class="mim-tip-reference" title="Lyko, F., Buiting, K., Horsthemke, B., Paro, R. <strong>Identification of a silencing element in the human 15q11-q13 imprinting center by using transgenic Drosophila.</strong> Proc. Nat. Acad. Sci. 95: 1698-1702, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9465079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9465079</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9465079[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.4.1698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9465079">Lyko et al. (1998)</a> showed that a fragment from this region can function as a silencer in transgenic flies. Repression was detected specifically from this element and could not be observed with control human sequences. Additional experiments allowed the delineation of the silencer to a fragment of 215 bp containing the SNRPN promoter region. These results provide an additional link between genomic imprinting and an evolutionarily conserved silencing mechanism. <a href="#16" class="mim-tip-reference" title="Lyko, F., Buiting, K., Horsthemke, B., Paro, R. <strong>Identification of a silencing element in the human 15q11-q13 imprinting center by using transgenic Drosophila.</strong> Proc. Nat. Acad. Sci. 95: 1698-1702, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9465079/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9465079</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9465079[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.4.1698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9465079">Lyko et al. (1998)</a> suggested that the identified element participates in the long-range regulation of the imprinted 15q11-q13 domain or locally represses SNRPN expression from the maternal allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9465079" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Schweizer, J., Zynger, D., Francke, U. <strong>In vivo nuclease hypersensitivity studies reveal multiple sites of parental origin-dependent differential chromatin conformation in the 150 kb SNRPN transcription unit.</strong> Hum. Molec. Genet. 8: 555-566, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10072422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10072422</a>] [<a href="https://doi.org/10.1093/hmg/8.4.555" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10072422">Schweizer et al. (1999)</a> studied the mechanism by which small microdeletions within the 5-prime region of the SNRPN transcription unit affect the transcriptional activity and methylation status of distant imprinted genes throughout 15q11-q13 in cis. They analyzed the chromatin structure of the 150-kb SNRPN transcription unit for DNaseI- and MspI-hypersensitive sites. Using an in vivo approach on lymphoblastoid cell lines from PWS and AS individuals, they discovered that exon 1 of the SNRPN gene is flanked by prominent hypersensitive sites on the paternal allele, but is completely inaccessible to nucleases on the maternal allele. In contrast, they identified several regions of increased nuclease hypersensitivity on the maternal allele, one of which coincides with the minimal microdeletion region for AS, and another that lies in intron 1 immediately downstream of the paternal-specific hypersensitive sites. At several sites, parental origin-specific nuclease hypersensitivity was found to be correlated with hypermethylation on the allele contributed by the other parent. <a href="#29" class="mim-tip-reference" title="Schweizer, J., Zynger, D., Francke, U. <strong>In vivo nuclease hypersensitivity studies reveal multiple sites of parental origin-dependent differential chromatin conformation in the 150 kb SNRPN transcription unit.</strong> Hum. Molec. Genet. 8: 555-566, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10072422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10072422</a>] [<a href="https://doi.org/10.1093/hmg/8.4.555" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10072422">Schweizer et al. (1999)</a> suggested that the differential parental origin-dependent chromatin conformations may govern access of regulatory protein complexes and/or RNAs that mediate interaction of the region with other genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10072422" 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>Several observations had suggested that cis elements within the AS-SRO (shortest region of overlap) and PWS-SRO constitute an imprinting box that regulates the entire domain on both chromosomes. <a href="#30" class="mim-tip-reference" title="Shemer, R., Hershko, A. Y., Perk, J., Mostoslavsky, R., Tsuberi, B., Cedar, H., Buiting, K., Razin, A. <strong>The imprinting box of the Prader-Willi/Angelman syndrome domain.</strong> Nature Genet. 26: 440-443, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11101841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11101841</a>] [<a href="https://doi.org/10.1038/82571" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11101841">Shemer et al. (2000)</a> showed that a minitransgene composed of 200-bp Snrpn promoter/exon 1 and a 1-kb sequence located approximately 35 kb upstream to the SNRPN promoter confer imprinting as judged by differential methylation, parent-of-origin-specific transcription, and asynchronous replication. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11101841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Geuns, E., De Rycke, M., Van Steirteghem, A., Liebaers, I. <strong>Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryos.</strong> Hum. Molec. Genet. 12: 2873-2879, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14500540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14500540</a>] [<a href="https://doi.org/10.1093/hmg/ddg315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14500540">Geuns et al. (2003)</a> studied the methylation patterns of the imprint control region of the SNRPN gene in human spermatozoa, oocytes at the germinal vesicle, metaphase I, and metaphase II stages, and preimplantation embryos. In spermatozoa, almost all potential methylation sites were unmethylated, whereas near-complete methylatation patterns were found in oocytes at all 3 developmental stages. In embryos, an average methylation pattern of 53% was found, indicating that the imprints, which had been set during gametogenesis, are stably maintained in the preimplantation embryo. <a href="#7" class="mim-tip-reference" title="Geuns, E., De Rycke, M., Van Steirteghem, A., Liebaers, I. <strong>Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryos.</strong> Hum. Molec. Genet. 12: 2873-2879, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14500540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14500540</a>] [<a href="https://doi.org/10.1093/hmg/ddg315" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14500540">Geuns et al. (2003)</a> concluded that the maternal imprints for the imprint control region of the SNRPN gene are already reestablished at the germinal vesicle stage, and are not reestablished in a late oocyte stage or after fertilization, as had been previously reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14500540" 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="Kantor, B., Kaufman, Y., Makedonski, K., Razin, A., Shemer, R. <strong>Establishing the epigenetic status of the Prader-Willi/Angelman imprinting center in the gametes and embryo.</strong> Hum. Molec. Genet. 13: 2767-2779, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15367489/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15367489</a>] [<a href="https://doi.org/10.1093/hmg/ddh290" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15367489">Kantor et al. (2004)</a> constructed a transgene including both the 4.3-kb PWS-SRO sequence and the 880-bp AS-SRO sequence and determined that the transgene carried out the entire imprinting process. The epigenetic features of this transgene resembled those previously observed on the endogenous locus, thus allowing analyses in mouse gametes and early embryos. In gametes, they identified a differentially methylated CpG cluster (DMR) on AS-SRO that was methylated in sperm and unmethylated in oocytes. This DMR specifically bound a maternal allele-discrimination protein that was involved in DMR maintenance through implantation when methylation of PWS-SRO the maternal allele takes place. While the AS-SRO was required in gametes to confer methylation on PWS-SRO, it was dispensable later in development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15367489" 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>The SNRPN 5-prime region colocalizes with the PWS imprinting center and contains 2 DNase I hypersensitive sites, DHS1 at the SNRPN promoter and DHS2 within intron 1, exclusively on the paternally inherited chromosome. <a href="#24" class="mim-tip-reference" title="Rodriguez-Jato, S., Nicholls, R. D, Driscoll, D. J., Yang, T. P. <strong>Characterization of cis- and trans-acting elements in the imprinted human SNURF-SNRPN locus.</strong> Nucleic Acids Res. 33: 4740-4753, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16116039/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16116039</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16116039[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/10.1093/nar/gki786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16116039">Rodriguez-Jato et al. (2005)</a> examined DHS1 and DHS2 to identify cis- and trans-acting regulatory elements within the endogenous SNRPN 5-prime region. Analysis of DHS1 by in vivo footprinting and chromatin immunoprecipitation identified allele-specific interactions with multiple regulatory proteins, including NRF1 (<a href="/entry/600879">600879</a>), which regulates genes involved in mitochondrial and metabolic functions. DHS2 acted as an enhancer of the SNRPN promoter and contained a highly conserved region that showed allele-specific interactions with unphosphorylated RNA polymerase II (see <a href="/entry/180660">180660</a>), YY1 (<a href="/entry/600013">600013</a>), Sp1 (<a href="/entry/189906">189906</a>), and NRF1, further suggesting a key role for NRF1 in regulation of the SNRPN locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16116039" 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 mouse and humans, several alternative exons expressed from upstream alternative promoters of the Snrpn gene are expressed as IC transcripts (<a href="#2" class="mim-tip-reference" title="Bressler, J., Tsai, T.-F., Wu, M.-Y., Tsai, S.-F., Ramirez, M. A., Armstrong, D., Beaudet, A. L. <strong>The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice.</strong> Nature Genet. 28: 232-240, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431693</a>] [<a href="https://doi.org/10.1038/90067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431693">Bressler et al., 2001</a>). However, there is no similarity between the nucleotide sequences of human and mouse IC transcripts. In mice, <a href="#17" class="mim-tip-reference" title="Mapendano, C. K., Kishino, T., Miyazaki, K., Kondo, S., Yoshiura, K., Hishikawa, Y., Koji, T., Niikawa, N., Ohta, T. <strong>Expression of the Snurf-Snrpn IC transcript in the oocyte and its putative role in the imprinting establishment of the mouse 7C imprinting domain.</strong> J. Hum. Genet. 51: 236-243, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429232</a>] [<a href="https://doi.org/10.1007/s10038-005-0351-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16429232">Mapendano et al. (2006)</a> found strong expression of Snrpn IC transcripts in brain and ovary but not in other tissues. Expression levels in the brain were 7-fold higher compared to those in ovaries. In situ hybridization signals were observed in oocytes and granulosa cells of the secondary and developing follicles. <a href="#17" class="mim-tip-reference" title="Mapendano, C. K., Kishino, T., Miyazaki, K., Kondo, S., Yoshiura, K., Hishikawa, Y., Koji, T., Niikawa, N., Ohta, T. <strong>Expression of the Snurf-Snrpn IC transcript in the oocyte and its putative role in the imprinting establishment of the mouse 7C imprinting domain.</strong> J. Hum. Genet. 51: 236-243, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16429232/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16429232</a>] [<a href="https://doi.org/10.1007/s10038-005-0351-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16429232">Mapendano et al. (2006)</a> suggested that the IC transcript may be associated with the establishment of PWS-IC methylation on the maternal chromosome as an AS-IC cis-acting element. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11431693+16429232" 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="#31" class="mim-tip-reference" title="Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G. <strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong> Hum. Molec. Genet. 5: 517-524, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845846</a>] [<a href="https://doi.org/10.1093/hmg/5.4.517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845846">Sun et al. (1996)</a> reported a patient with the PWS phenotype and a balanced reciprocal translocation t(15;19)(q12;q13.41), which was paternal in origin. By FISH analysis and examination of DNA by Southern blot hybridization, they found that the translocation breakpoint occurred between exons 0 and 1 of the SNRPN locus, outside of the SmN open reading frame. <a href="#31" class="mim-tip-reference" title="Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G. <strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong> Hum. Molec. Genet. 5: 517-524, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845846</a>] [<a href="https://doi.org/10.1093/hmg/5.4.517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845846">Sun et al. (1996)</a> reported that the transcriptional activities of ZNF127 (MKRN3; <a href="/entry/603856">603856</a>), IPW, PAR1 (<a href="/entry/600161">600161</a>), and PAR5 (<a href="/entry/600162">600162</a>) were detected with RT-PCR from fibroblasts of this patient, whereas transcription from only the first 2 exons and the last 7 exons of SNRPN was detected with RT-PCR. The complete SNRPN mRNA (10 exons) was not detected. <a href="#31" class="mim-tip-reference" title="Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G. <strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong> Hum. Molec. Genet. 5: 517-524, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845846</a>] [<a href="https://doi.org/10.1093/hmg/5.4.517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845846">Sun et al. (1996)</a> suggested that the putative SNURF sequence would be interrupted in this patient, and this disruption may play a role in the etiology of the PWS phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845846" 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="#12" class="mim-tip-reference" title="Kuslich, C. D., Kobori, J. A., Mohapatra, G., Gregorio-King, C., Donlon, T. A. <strong>Prader-Willi syndrome is caused by disruption of the SNRPN gene.</strong> Am. J. Hum. Genet. 64: 70-76, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9915945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9915945</a>] [<a href="https://doi.org/10.1086/302177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9915945">Kuslich et al. (1999)</a> likewise identified a de novo balanced translocation in a Prader-Willi syndrome patient: (4;15)(q27;q11.2)pat. The breakpoints lay between SNRPN exons 2 and 3. Parental-origin studies indicated that there was no uniparental disomy and no apparent deletion. The patient expressed ZNF127, SNRPN exons 1 and 2, IPW, and PAR1, but did not express either SNRPN exons 3 and 4 or PAR5, as assayed by RT-PCR, of peripheral blood cells. <a href="#12" class="mim-tip-reference" title="Kuslich, C. D., Kobori, J. A., Mohapatra, G., Gregorio-King, C., Donlon, T. A. <strong>Prader-Willi syndrome is caused by disruption of the SNRPN gene.</strong> Am. J. Hum. Genet. 64: 70-76, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9915945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9915945</a>] [<a href="https://doi.org/10.1086/302177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9915945">Kuslich et al. (1999)</a> concluded that this patient and that reported by <a href="#31" class="mim-tip-reference" title="Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G. <strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong> Hum. Molec. Genet. 5: 517-524, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845846</a>] [<a href="https://doi.org/10.1093/hmg/5.4.517" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845846">Sun et al. (1996)</a> supported the contention that an intact genomic region and/or transcription of SNRPN exons 2 and 3 play a pivotal role in the manifestations of the major clinical phenotype in PWS. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8845846+9915945" 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="#28" class="mim-tip-reference" title="Schulze, A., Hansen, C., Skakkebaek, N. E., Brondum-Nielsen, K., Ledbetter, D. H., Tommerup, N. <strong>Exclusion of SNRPN as a major determinant of Prader-Willi syndrome by a translocation breakpoint.</strong> Nature Genet. 12: 452-454, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630505</a>] [<a href="https://doi.org/10.1038/ng0496-452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8630505">Schulze et al. (1996)</a> presented evidence suggesting that SNRPN is not a major determinant of the Prader-Willi syndrome. They mapped the breakpoint of balanced translocation (9;15)pat associated with most of the PWS features to a region between SNRPN and PAR1. Methylation and expression studies indicated that the paternal SNRPN allele was unaffected by the translocation, while IPW and PAR1 were unexpressed. This focused attention on genes distal to the breakpoint as the main candidate for PWS genes and was considered consistent with a cis action of the putative imprinting center (IC) gene located proximal to SNRPN (<a href="#32" class="mim-tip-reference" title="Sutcliffe, J. S., Nakao, M., Christian, S., Orstavik, K. H., Tommerup, N., Ledbetter, D. H., Beaudet, A. L. <strong>Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region.</strong> Nature Genet. 8: 52-58, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7987392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7987392</a>] [<a href="https://doi.org/10.1038/ng0994-52" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7987392">Sutcliffe et al., 1994</a>; <a href="#3" class="mim-tip-reference" title="Buiting, K., Saitoh, S., Gross, S., Dittrich, B., Schwartz, S., Nicholls, R. D., Horsthemke, B. <strong>Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15.</strong> Nature Genet. 9: 395-400, 1995. Note: Erratum: Nature Genet. 10: 249 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795645</a>] [<a href="https://doi.org/10.1038/ng0495-395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7795645">Buiting et al., 1995</a>). <a href="#28" class="mim-tip-reference" title="Schulze, A., Hansen, C., Skakkebaek, N. E., Brondum-Nielsen, K., Ledbetter, D. H., Tommerup, N. <strong>Exclusion of SNRPN as a major determinant of Prader-Willi syndrome by a translocation breakpoint.</strong> Nature Genet. 12: 452-454, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630505</a>] [<a href="https://doi.org/10.1038/ng0496-452" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8630505">Schulze et al. (1996)</a> suggested that further studies of translocational disruption of the imprinted region may establish genotype/phenotype relationships in Prader-Willi syndrome, which they presumed to be a contiguous gene syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8630505+7795645+7987392" 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>Balanced translocations affecting the paternal copy of 15q11-q13 have been proven to be a rare cause of Prader-Willi syndrome (PWS) or PWS-like features. <a href="#35" class="mim-tip-reference" title="Wirth, J., Back, E., Huttenhofer, A., Nothwang, H.-G., Lich, C., Gross, S., Menzel, C,, Schinzel, A., Kioschis, P., Tommerup, N., Ropers, H.-H., Horsthemke, B., Buiting, K. <strong>A translocation breakpoint cluster disrupts the newly defined 3-prime end of the SNURF-SNRPN transcription unit on chromosome 15.</strong> Hum. Molec. Genet. 10: 201-210, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11159938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11159938</a>] [<a href="https://doi.org/10.1093/hmg/10.3.201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11159938">Wirth et al. (2001)</a> reported a de novo balanced reciprocal translocation, t(X;15)(q28;q12), in a female patient with atypical PWS. The translocation breakpoints in this patient and 2 previously reported patients mapped 70 to 80 kb distal to the SNURF-SNRPN gene and defined a breakpoint cluster region. The breakpoints disrupted one of several previously unknown 3-prime exons of this gene. RT-PCR experiments demonstrated that sequences distal to the breakpoint, including the C/D box snoRNA gene cluster HBII-85, as well as IPW and PAR1, were not expressed in the patient. The authors suggested that lack of expression of these sequences may contribute to the PWS phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11159938" 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="Gallagher, R. C., Pils, B., Albalwi, M., Francke, U. <strong>Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader-Willi syndrome.</strong> Am. J. Hum. Genet. 71: 669-678, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12154412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12154412</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12154412[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/342408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12154412">Gallagher et al. (2002)</a> suggested that the minimal critical region for PWS is approximately 121 kb within the SNRPN locus of more than 460 kb, bordered by a breakpoint cluster region identified in 3 individuals with PWS who had balanced reciprocal translocations and by the proximal deletion breakpoint of a familial deletion found in an unaffected mother, her 3 children with AS, and her father. The subset of SNRPN-encoded snoRNAs within this region comprises the PWCR1/HBII-85 (SNORD116-1; <a href="/entry/605436">605436</a>) cluster of snoRNAs and the single HBII-438A snoRNA. These are the only known genes within this region, which suggests that loss of their expression may be responsible for much or all of the phenotype of PWS. This hypothesis is challenged by findings in 2 individuals with PWS who had balanced translocations with breakpoints upstream of the proposed minimal critical region but whose cells were reported to express transcripts within it, adjacent to these snoRNAs. By use of real-time quantitative RT-PCR, <a href="#6" class="mim-tip-reference" title="Gallagher, R. C., Pils, B., Albalwi, M., Francke, U. <strong>Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader-Willi syndrome.</strong> Am. J. Hum. Genet. 71: 669-678, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12154412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12154412</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12154412[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/342408" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12154412">Gallagher et al. (2002)</a> reassessed expression of these transcripts and of the snoRNAs themselves in fibroblasts of 1 of these patients. They found that the transcripts reported to be expressed in lymphoblast-somatic cell hybrids were not expressed in fibroblasts, and they suggested that the original results were misinterpreted. Most important, they showed that the PWCR1/HBII-85 snoRNAs were not expressed in fibroblasts of this individual. These results were consistent with the hypothesis that loss of expression of the snoRNAs in the proposed minimal critical region confers much or all of the phenotype of PWS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12154412" 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 2 sibs with the typical phenotype of PWS but without a cytogenetically detectable deletion in 15q, <a href="#10" class="mim-tip-reference" title="Ishikawa, T., Kibe, T., Wada, Y. <strong>Deletion of small nuclear ribonucleoprotein polypeptide N (SNRPN) in Prader-Willi syndrome detected by fluorescence in situ hybridization: two sibs with the typical phenotype without a cytogenetic deletion in chromosome 15q.</strong> Am. J. Med. Genet. 62: 350-352, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8723064/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8723064</a>] [<a href="https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4<350::AID-AJMG6>3.0.CO;2-V" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8723064">Ishikawa et al. (1996)</a> demonstrated deletion of SNRPN by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8723064" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Bielinska, B., Blaydes, S. M., Buiting, K., Yang, T., Krajewska-Walasek, M., Horsthemke, B., Brannan, C. I. <strong>De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch.</strong> Nature Genet. 25: 74-78, 2000. Note: Erratum: Nature Genet. 25: 241 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802660</a>] [<a href="https://doi.org/10.1038/75629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802660">Bielinska et al. (2000)</a> reported a PWS family in which the father was mosaic for an imprinting center deletion on his paternal chromosome. The deletion chromosome had acquired a maternal methylation imprint in his somatic cells. Identical observations were made in chimeric mice generated from 2 independent embryonic stem cell lines harboring a similar deletion. <a href="#1" class="mim-tip-reference" title="Bielinska, B., Blaydes, S. M., Buiting, K., Yang, T., Krajewska-Walasek, M., Horsthemke, B., Brannan, C. I. <strong>De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch.</strong> Nature Genet. 25: 74-78, 2000. Note: Erratum: Nature Genet. 25: 241 only, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802660</a>] [<a href="https://doi.org/10.1038/75629" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10802660">Bielinska et al. (2000)</a> concluded that the Prader-Willi syndrome imprinting center element is not only required for the establishment of the paternal imprint, but also for its postzygotic maintenance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802660" 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>The SNRPN promoter is embedded in a CpG island that is maternally methylated, is expressed only from the paternal chromosome, and lies within an imprinting center that is required for switching to and/or maintenance of the paternal epigenotype. In mice and humans, the SNRPN gene, as well as other loci in the region, are subject to genomic imprinting. <a href="#2" class="mim-tip-reference" title="Bressler, J., Tsai, T.-F., Wu, M.-Y., Tsai, S.-F., Ramirez, M. A., Armstrong, D., Beaudet, A. L. <strong>The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice.</strong> Nature Genet. 28: 232-240, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431693</a>] [<a href="https://doi.org/10.1038/90067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11431693">Bressler et al. (2001)</a> showed that a 0.9-kb deletion of exon 1 of mouse Snrpn did not disrupt imprinting or elicit any obvious phenotype, although it did allow the detection of previously unknown upstream exons. In contrast, a larger, overlapping 4.8-kb deletion caused a partial or mosaic imprinting defect and perinatal lethality when paternally inherited. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11431693" 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>As part of studies of genomic imprinting in the Prader-Willi/Angelman domain, <a href="#33" class="mim-tip-reference" title="Tsai, T.-F., Chen, K.-S., Weber, J. S., Justice, M. J., Beaudet, A. L. <strong>Evidence for translational regulation of the imprinted Snurf-Snrpn locus in mice.</strong> Hum. Molec. Genet. 11: 1659-1668, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075010</a>] [<a href="https://doi.org/10.1093/hmg/11.14.1659" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12075010">Tsai et al. (2002)</a> inserted an agouti coat color cassette into the downstream open reading frame (ORF) of the Snurf-Snrpn locus in the mouse. The fusion gene was maternally silenced, as is Snurf-Snrpn, and produced a tan abdomen only when inherited paternally in otherwise black mice. A screen for dominant epigenetic or genetic events was performed with ENU mutagenesis, using a strategy whereby variation in abdominal color was scored at weaning. One mouse with maternal origin of the fusion gene had a tan abdomen and had an imprinting defect resulting in loss of both maternal methylation and silencing of the fusion gene. One mouse with paternal origin of the fusion gene was completely yellow and was found to have an ATG-to-AAG mutation in the initiation codon of the upstream ORF encoding Snurf. Northern blotting, immunoblotting, and transfection studies demonstrated that the mutation caused a 15-fold increase in translation of the downstream ORF in 2 fusion constructs, leading the authors to suggest that similar translational control may affect the normal Snurf-Snrpn transcript as well. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12075010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Peery, E. G., Elmore, M. D., Resnick, J. L., Brannan, C. I., Johnstone, K. A. <strong>A targeted deletion upstream of Snrpn does not result in an imprinting defect.</strong> Mammalian Genome 18: 255-262, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17514346/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17514346</a>] [<a href="https://doi.org/10.1007/s00335-007-9019-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17514346">Peery et al. (2007)</a> generated 2 deletions in mouse at a location analogous to that of the human AS-IC upstream of the SNRPN gene. Neither deletion produced an imprinting defect, suggesting that the location of the AS-IC is not strictly conserved between human and mouse. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17514346" 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>Superovulation (ovarian stimulation) is an assisted reproductive technology (ART) for human subfertility/infertility treatment, which has been correlated with increased frequencies of imprinting disorders such as Angelman (<a href="/entry/105830">105830</a>) and Beckwith-Wiedemann syndromes (<a href="/entry/130650">130650</a>). <a href="#18" class="mim-tip-reference" title="Market-Velker, B. A., Zhang, L., Magri, L. S., Bonvissuto, A. C., Mann, M. R. W. <strong>Dual effects of superovulation: loss of maternal and paternal imprinted methylation in a dose-dependent manner.</strong> Hum. Molec. Genet. 19: 36-51, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19805400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19805400</a>] [<a href="https://doi.org/10.1093/hmg/ddp465" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19805400">Market-Velker et al. (2010)</a> examined the effects of superovulation on genomic imprinting in individual mouse blastocyst stage embryos. Superovulation perturbed genomic imprinting of both maternally and paternally expressed genes. Loss of Snrpn, Peg3 (<a href="/entry/601483">601483</a>), and Kcnq1ot1 (<a href="/entry/604115">604115</a>) and gain of H19 (<a href="/entry/103280">103280</a>) imprinted methylation were observed. This perturbation was dose-dependent, with aberrant imprinted methylation more frequent at higher hormone dosage. Maternal as well as paternal H19 methylation was perturbed by superovulation. <a href="#18" class="mim-tip-reference" title="Market-Velker, B. A., Zhang, L., Magri, L. S., Bonvissuto, A. C., Mann, M. R. W. <strong>Dual effects of superovulation: loss of maternal and paternal imprinted methylation in a dose-dependent manner.</strong> Hum. Molec. Genet. 19: 36-51, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19805400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19805400</a>] [<a href="https://doi.org/10.1093/hmg/ddp465" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19805400">Market-Velker et al. (2010)</a> postulated that superovulation may have dual effects during oogenesis, disrupting acquisition of imprints in growing oocytes, as well as maternal-effect gene products subsequently required for imprint maintenance during preimplantation development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19805400" 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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Bielinska, B., Blaydes, S. M., Buiting, K., Yang, T., Krajewska-Walasek, M., Horsthemke, B., Brannan, C. I.
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<strong>De novo deletions of SNRPN exon 1 in early human and mouse embryos result in a paternal to maternal imprint switch.</strong>
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Nature Genet. 25: 74-78, 2000. Note: Erratum: Nature Genet. 25: 241 only, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10802660/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10802660</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10802660" 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/10.1038/75629" target="_blank">Full Text</a>]
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Bressler, J., Tsai, T.-F., Wu, M.-Y., Tsai, S.-F., Ramirez, M. A., Armstrong, D., Beaudet, A. L.
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<strong>The SNRPN promoter is not required for genomic imprinting of the Prader-Willi/Angelman domain in mice.</strong>
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Nature Genet. 28: 232-240, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11431693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11431693</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11431693" 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/10.1038/90067" target="_blank">Full Text</a>]
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Buiting, K., Saitoh, S., Gross, S., Dittrich, B., Schwartz, S., Nicholls, R. D., Horsthemke, B.
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<strong>Inherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15.</strong>
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Nature Genet. 9: 395-400, 1995. Note: Erratum: Nature Genet. 10: 249 only, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795645/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795645</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795645" 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/ng0495-395" target="_blank">Full Text</a>]
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Cattanach, B. M., Barr, J. A., Evans, E. P., Burtenshaw, M., Beechey, C. V., Leff, S. E., Brannan, C. I., Copeland, N. G., Jenkins, N. A., Jones, J.
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<strong>A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression.</strong>
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Nature Genet. 2: 270-274, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1303278/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1303278</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1303278" 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/ng1292-270" target="_blank">Full Text</a>]
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Dittrich, B., Buiting, K., Korn, B., Rickard, S., Buxton, J., Saitoh, S., Nicholls, R. D., Poustka, A., Winterpacht, A., Zabel, B., Horsthemke, B.
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<strong>Imprint switching on human chromosome 15 may involve alternative transcripts of the SNRPN gene.</strong>
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Nature Genet. 14: 163-170, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8841186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8841186</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8841186" 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/ng1096-163" target="_blank">Full Text</a>]
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Gallagher, R. C., Pils, B., Albalwi, M., Francke, U.
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<strong>Evidence for the role of PWCR1/HBII-85 C/D box small nucleolar RNAs in Prader-Willi syndrome.</strong>
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Am. J. Hum. Genet. 71: 669-678, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12154412/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12154412</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12154412[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=12154412" 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/10.1086/342408" target="_blank">Full Text</a>]
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Geuns, E., De Rycke, M., Van Steirteghem, A., Liebaers, I.
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<strong>Methylation imprints of the imprint control region of the SNRPN-gene in human gametes and preimplantation embryos.</strong>
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Hum. Molec. Genet. 12: 2873-2879, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14500540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14500540</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14500540" 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/ddg315" target="_blank">Full Text</a>]
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Glenn, C. C., Porter, K. A., Jong, M. T. C., Nicholls, R. D., Driscoll, D. J.
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<strong>Functional imprinting and epigenetic modification of the human SNRPN gene.</strong>
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Hum. Molec. Genet. 2: 2001-2005, 1993.
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[<a href="https://doi.org/10.1093/hmg/2.12.2001" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.96.10.5616" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1096-8628(19960424)62:4<350::AID-AJMG6>3.0.CO;2-V" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/ddh290" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/302177" target="_blank">Full Text</a>]
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Runte, M., Huttenhofer, A., Gross, S., Kiefmann, M., Horsthemke, B., Buiting, K.
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<strong>The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A.</strong>
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Hum. Molec. Genet. 10: 2687-2700, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11726556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11726556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11726556" 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/10.23.2687" target="_blank">Full Text</a>]
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Saitoh, S., Wada, T.
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<strong>Parent-of-origin specific histone acetylation and reactivation of a key imprinted gene locus in Prader-Willi syndrome.</strong>
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Am. J. Hum. Genet. 66: 1958-1962, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10775525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10775525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10775525" 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/10.1086/302917" target="_blank">Full Text</a>]
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Schmauss, C., McAllister, G., Ohosone, Y., Hardin, J. A., Lerner, M. R.
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<strong>A comparison of snRNP-associated Sm-autoantigens: human N, rat N and human B/B-prime.</strong>
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Nucleic Acids Res. 17: 1733-1743, 1989. Note: Erratum: Nucleic Acids Res. 17: 6777 only, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2522186/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2522186</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2522186" 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/nar/17.4.1733" target="_blank">Full Text</a>]
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Schulze, A., Hansen, C., Skakkebaek, N. E., Brondum-Nielsen, K., Ledbetter, D. H., Tommerup, N.
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<strong>Exclusion of SNRPN as a major determinant of Prader-Willi syndrome by a translocation breakpoint.</strong>
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Nature Genet. 12: 452-454, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8630505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8630505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8630505" 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/ng0496-452" target="_blank">Full Text</a>]
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Schweizer, J., Zynger, D., Francke, U.
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<strong>In vivo nuclease hypersensitivity studies reveal multiple sites of parental origin-dependent differential chromatin conformation in the 150 kb SNRPN transcription unit.</strong>
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Hum. Molec. Genet. 8: 555-566, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10072422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10072422</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10072422" 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/8.4.555" target="_blank">Full Text</a>]
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Shemer, R., Hershko, A. Y., Perk, J., Mostoslavsky, R., Tsuberi, B., Cedar, H., Buiting, K., Razin, A.
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<strong>The imprinting box of the Prader-Willi/Angelman syndrome domain.</strong>
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Nature Genet. 26: 440-443, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11101841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11101841</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11101841" 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/10.1038/82571" target="_blank">Full Text</a>]
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Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G.
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<strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong>
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Hum. Molec. Genet. 5: 517-524, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845846/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845846</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845846" 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/5.4.517" target="_blank">Full Text</a>]
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Sutcliffe, J. S., Nakao, M., Christian, S., Orstavik, K. H., Tommerup, N., Ledbetter, D. H., Beaudet, A. L.
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<strong>Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region.</strong>
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Nature Genet. 8: 52-58, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7987392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7987392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7987392" 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/ng0994-52" target="_blank">Full Text</a>]
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Tsai, T.-F., Chen, K.-S., Weber, J. S., Justice, M. J., Beaudet, A. L.
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<strong>Evidence for translational regulation of the imprinted Snurf-Snrpn locus in mice.</strong>
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Hum. Molec. Genet. 11: 1659-1668, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12075010/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12075010</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12075010" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Wawrzik, M., Spiess, A.-N., Herrmann, R., Buiting, K., Horsthemke, B.
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<strong>Expression of SNURF-SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis.</strong>
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Europ. J. Hum. Genet. 17: 1463-1470, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19471314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19471314</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19471314[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=19471314" 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.2009.83" target="_blank">Full Text</a>]
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Wirth, J., Back, E., Huttenhofer, A., Nothwang, H.-G., Lich, C., Gross, S., Menzel, C,, Schinzel, A., Kioschis, P., Tommerup, N., Ropers, H.-H., Horsthemke, B., Buiting, K.
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<strong>A translocation breakpoint cluster disrupts the newly defined 3-prime end of the SNURF-SNRPN transcription unit on chromosome 15.</strong>
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Hum. Molec. Genet. 10: 201-210, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11159938/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11159938</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11159938" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Patricia A. Hartz - updated : 3/10/2015
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Patricia A. Hartz - updated : 8/15/2014<br>George E. Tiller - updated : 11/12/2010<br>Patricia A. Hartz - updated : 8/28/2009<br>Patricia A. Hartz - updated : 11/29/2007<br>George E. Tiller - updated : 5/30/2007<br>Matthew B. Gross - reorganized : 5/16/2006<br>Matthew B. Gross - updated : 5/16/2006<br>Cassandra L. Kniffin - updated : 4/28/2006<br>George E. Tiller - updated : 1/11/2006<br>George E. Tiller - updated : 6/2/2003<br>Victor A. McKusick - updated : 10/7/2002<br>Victor A. McKusick - updated : 6/25/2001<br>George E. Tiller - updated : 4/17/2001<br>Victor A. McKusick - updated : 7/26/2000<br>Ada Hamosh - updated : 4/28/2000<br>Victor A. McKusick - updated : 6/2/1999<br>Victor A. McKusick - updated : 5/14/1999<br>Victor A. McKusick - updated : 2/8/1999<br>Victor A. McKusick - updated : 3/5/1998<br>Moyra Smith - updated : 10/2/1996<br>Moyra Smith - updated : 5/14/1996
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Victor A. McKusick : 1/26/1993
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mcolton : 3/10/2015<br>mgross : 8/18/2014<br>mgross : 8/15/2014<br>mcolton : 8/15/2014<br>mcolton : 8/15/2014<br>terry : 9/17/2012<br>wwang : 11/18/2010<br>terry : 11/12/2010<br>wwang : 3/11/2010<br>mgross : 9/15/2009<br>terry : 8/28/2009<br>wwang : 4/29/2008<br>terry : 4/25/2008<br>mgross : 11/30/2007<br>terry : 11/29/2007<br>wwang : 5/30/2007<br>mgross : 5/16/2006<br>mgross : 5/16/2006<br>mgross : 5/16/2006<br>wwang : 5/5/2006<br>ckniffin : 4/28/2006<br>carol : 4/6/2006<br>ckniffin : 3/20/2006<br>mgross : 1/23/2006<br>wwang : 1/23/2006<br>wwang : 1/20/2006<br>terry : 1/11/2006<br>cwells : 6/2/2003<br>carol : 10/7/2002<br>tkritzer : 10/7/2002<br>alopez : 6/28/2001<br>terry : 6/25/2001<br>cwells : 4/26/2001<br>cwells : 4/20/2001<br>cwells : 4/17/2001<br>cwells : 4/17/2001<br>carol : 11/28/2000<br>terry : 11/22/2000<br>terry : 11/22/2000<br>carol : 8/1/2000<br>terry : 7/26/2000<br>alopez : 6/9/2000<br>alopez : 5/1/2000<br>terry : 4/28/2000<br>mgross : 10/21/1999<br>carol : 6/8/1999<br>jlewis : 6/8/1999<br>jlewis : 6/8/1999<br>terry : 6/2/1999<br>mgross : 5/25/1999<br>mgross : 5/19/1999<br>terry : 5/14/1999<br>carol : 2/14/1999<br>terry : 2/8/1999<br>alopez : 3/24/1998<br>terry : 3/5/1998<br>terry : 7/7/1997<br>mark : 11/7/1996<br>terry : 10/3/1996<br>terry : 10/2/1996<br>mark : 10/2/1996<br>mark : 8/14/1996<br>carol : 5/14/1996<br>terry : 4/19/1996<br>mark : 4/9/1996<br>terry : 4/5/1996<br>mimadm : 3/25/1995<br>terry : 5/5/1994<br>carol : 3/11/1994<br>carol : 1/26/1993
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SMALL NUCLEAR RIBONUCLEOPROTEIN POLYPEPTIDE N; SNRPN
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<em>Alternative titles; symbols</em>
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SMN
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Other entities represented in this entry:
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SNRPN UPSTREAM READING FRAME, INCLUDED; SNURF, INCLUDED
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<strong><em>HGNC Approved Gene Symbol: SNRPN</em></strong>
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Cytogenetic location: 15q11.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 15:24,823,637-24,978,723 </span>
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<span class="small">(from NCBI)</span>
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>SNRPN, or SNURF-SNRPN, is a bicistronic imprinted gene that encodes 2 polypeptides, the SmN splicing factor, which is involved in RNA processing, and the SNRPN upstream reading frame (SNURF) polypeptide. The SNRPN gene is transcribed exclusively from the paternally inherited chromosome and shows highest expression in brain and heart. SNRPN is located within an imprinted gene cluster in chromosome 15 that is associated with Prader-Willi syndrome (PWS; 176270) and Angelman syndrome (AS; 105830), 2 clinically distinct neurogenetic disorders. PWS arises from loss of function of genes in this region expressed exclusively from the paternal chromosome, suggesting that SNRPN may play a role in its etiology (Rodriguez-Jato et al., 2005). </p>
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<strong>Cloning and Expression</strong>
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<p>Small nuclear ribonucleoprotein particles (snRNP) found in spliceosomes contain small RNAs U1 (180680), U2 (180690), U4, U5 (180691), and U6 (180692), and associated polypeptides. Some of these polypeptides are present in all 5 of these snRNPs and others are unique to U1 or U2 snRNPs or have tissue-limited expression patterns. SnRNP-associated proteins have epitopes that react with autoimmune sera. With such an antiserum (Sm), a protein termed SmN was identified and the gene subsequently cloned (McAllister et al., 1988; Li et al., 1989; Schmauss et al., 1989). Although the sequence of SmN shows it to be highly homologous to the ubiquitous core snRNP protein B and its alternatively spliced form B-prime, Ozcelik et al. (1992) noted that SmN is expressed predominantly in brain and especially in central neurons. They suggested that SmN may be involved in brain-specific mRNA splicing. </p><p><strong><em>SNRPN Upstream Reading Frame (SNURF)</em></strong></p><p>
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Sun et al. (1996) reported a patient with PWS phenotype and a balanced reciprocal translocation t(15;19)(q12;q13.41) of paternal origin in which the breakpoint occurred between exons 0 and 1 of the SNRPN locus, outside of the SmN open reading frame. Based on their findings, Sun et al. (1996) suggested that the 3 upstream exons (exons -1, 0, and 1) of SNRPN encode an additional independent reading frame, SNURF (SNRPN upstream reading frame). </p><p>Polycistronic transcripts are common in prokaryotes but rare in eukaryotes. Gray et al. (1999) found that 5 eutherian mammals (cow, rat, mouse, rabbit, and human) have the highly conserved SNURF coding sequence. The vast majority of nucleotide substitutions in SNURF were found to be in the wobble codon position, providing strong evolutionary evidence for selection for protein-coding function. Because SNURF-SNRPN maps to human chromosome 15q11-q13 and is paternally expressed, each cistron is a candidate for a role in the imprinted PWS and PWS mouse models. SNURF encodes a highly basic 71-amino acid protein that is nuclear-localized (as is the product of the SNRPN gene). Because SNURF is the only protein-coding sequence within the imprinting regulatory region in 15q11-q13, it may have provided the original selection for imprinting in this domain. Whereas some human tissues express a minor SNURF-only transcript, mouse tissues express only the bicistronic Snurf-Snrpn transcript. Gray et al. (1999) showed that both SNURF and SNRPN are translated in normal, but not PWS, human and mouse tissues and cell lines. These findings identified SNURF as a protein that is produced along with SNRPN from a bicistronic transcript; polycistronic mRNAs, therefore, are encoded in mammalian genomes where they may form functional operons. </p><p>By database analysis, Wawrzik et al. (2009) identified several novel transcripts from the SNURF-SNRPN region, 1 of which included exon 23 from the upstream PWRN1 gene (611215). Exon connection PCR analysis of fetal brain and testis detected 4 transcripts, including 2 that showed splicing between a 3-prime PWRN1 exon and SNURF-SNRPN exons. Wawrzik et al. (2009) suggested that PWNR1 is not an independent gene, but an alternative 5-prime part of SNURF-SNRPN. They also identified a transcript of unknown identity from this region, represented in GenBank as BC035402, that was upregulated in testis at meiosis. </p><p><strong><em>UBE3A Antisense Transcript</em></strong></p><p>
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Runte et al. (2001) reported that a long processed antisense transcript of UBE3A (601623) starts at the imprinting center (IC) at the 5-prime end of the SNURF-SNRPN gene. For further information on this antisense transcript, see SNHG14 (616259). </p>
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<strong>Gene Structure</strong>
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<p>Runte et al. (2001) determined that the SNURF-SNRPN core gene has 10 exons. Exons 1 through 3 encode SNURF, and exons 4 through 10 encode SNRPN. Upstream exon U5 includes the AS-IC element, whereas exon 1 includes the PWS-IC element. </p><p>For further information on the transcriptional unit that includes SNURF-SNRPN, see SNHG14 (616259).</p>
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<strong>Mapping</strong>
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<p>By study of somatic cell hybrids and hybrid cell lines, Ozcelik et al. (1992) mapped the SNRPN gene to chromosome 15q12 and a processed pseudogene, SNRPNP1, to chromosome 6pter-p21. Furthermore, they showed that SNRPN maps to the minimal deletion interval that is critical for Prader-Willi syndrome. </p><p>Mutirangura et al. (1993) constructed a complete YAC contig of the Prader-Willi/Angelman syndrome chromosome region and localized the SNRPN gene to specific YACs within the contig. </p><p>Leff et al. (1992) showed that the mouse Snrpn gene maps to chromosome 7 in a region of homology with human chromosome 15q11-q13. </p>
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<strong>Gene Function</strong>
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<p><strong><em>Imprinting of SNRPN</em></strong></p><p>
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Leff et al. (1992) demonstrated that the Snrpn gene is maternally imprinted in the mouse, suggesting that loss of the paternally derived SNRPN allele may be involved in the PWS phenotype. Cattanach et al. (1992) reported observations indicating that maternal duplication of the central part of mouse chromosome 7, where the Snrpn gene is located, causes an imprinting effect that may correspond to PWS. Paternal duplication was not associated with any detectable effect that might correspond with Angelman syndrome. </p><p>Glenn et al. (1993) demonstrated functional imprinting of the human SNRPN gene using RT-PCR. No expression was observed in cultured skin fibroblasts of patients with Prader-Willi syndrome but was found in all patients with Angelman syndrome and in normal controls. Glenn et al. (1993) also demonstrated a parent-specific DNA methylation imprint within intron 5 of the SNRPN gene, which suggested an epigenetic mechanism by which parent-specific expression of this gene might be inherited. Thus, the authors found that the pattern of imprinting fulfills 1 major criterion for SNRPN being involved in pathogenesis of PWS. </p><p>Reed and Leff (1994) characterized a sequence polymorphism within expressed portions of the human SNRPN gene and showed that the SNRPN gene is monoallelically expressed in fetal brain and heart and in adult brain. Analysis of maternal DNA and of SNRPN cDNA confirmed that the maternal allele is not expressed in fetal brain and heart. Thus, maternal imprinting of SNRPN supports the hypothesis that paternal absence of SNRPN is responsible for the PWS phenotype. </p><p>To examine the chromatin basis of imprinting in the 15q11-q13 region, Saitoh and Wada (2000) investigated the status of histone acetylation of the SNURF-SNRPN locus, which is a key imprinted gene in PWS. Chromatin immunoprecipitation studies showed that the unmethylated CpG island of the active, paternally derived allele associated with acetylated histones, whereas the methylated maternally derived, inactive allele was specifically hypoacetylated. The body of the SNURF-SNRPN gene was associated with acetylated histones on both alleles. Treatment of PWS cells with the DNA methyltransferase inhibitor 5-azadeoxycytidine induced demethylation of the SNURF-SNRPN CpG island and restored gene expression on the maternal allele. The reactivation was associated with increased H4 acetylation but not with H3 acetylation at the SNURF-SNRPN CpG island. These findings indicated that (1) a significant role for histone deacetylation in gene silencing is associated with imprinting in 15q11-q13, and (2) silenced genes in PWS can be reactivated by drug treatment. Thus, the potential for pharmaceutical treatment of imprinting-related disorders was raised. </p><p>Using Zfp57 (612192) mutant mice, Li et al. (2008) found that Zfp57 was required for maternal imprinting at the Snrpn locus in the female germline. </p><p><strong><em>SNRPN-Associated Imprinting Center</em></strong></p><p>
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Dittrich et al. (1996) reported the existence of an imprinting center, which maps to a 100-kb region of chromosome 15q11-q13. This imprinting center encodes alternative transcripts of the SNRPN gene. The novel exons lack protein coding potential and are expressed from the paternal chromosome only. They also reported that families with imprinting mutations have mutations in this transcription unit. Deletions and point mutations of the alternative 5-prime exons of SNRPN (referred to as BD transcripts) are associated with a block of the maternal-paternal imprint switch in several families with Angelman syndrome. Deletions of SNRPN exon 1 are associated with a block of the maternal-paternal imprint switch in several families with Prader-Willi syndrome. Based on their studies, Dittrich et al. (1996) proposed a model for imprint switching. In this model the imprint center consists of an imprinter and an imprint switch initiation site. The imprinter encodes the BD transcript. They proposed that the imprinter is transcribed from the paternal chromosome only and that it acts in cis on the switch initiation site (the SNRPN promoter, exon 1, or a site close by), possibly by introducing a change in chromatin structure. </p><p>Prader-Willi syndrome and Angelman syndrome are neurogenetic disorders caused by the lack of a paternal or a maternal contribution from human 15q11-q13, respectively. They involve oppositely imprinted genes: the paternally expressed PWS gene(s) and the maternally expressed AS gene. Deletions in the transcription unit of the imprinted SNRPN gene occur in patients who have PWS or Angelman syndrome because of a parental imprint switch failure in this chromosomal domain. It has been suggested that the SNRPN exon 1 region, which is deleted in PWS patients, contains an imprint switch element from which the maternal and paternal epigenotypes of the 15q11-q13 domain originate. Using the model organism Drosophila, Lyko et al. (1998) showed that a fragment from this region can function as a silencer in transgenic flies. Repression was detected specifically from this element and could not be observed with control human sequences. Additional experiments allowed the delineation of the silencer to a fragment of 215 bp containing the SNRPN promoter region. These results provide an additional link between genomic imprinting and an evolutionarily conserved silencing mechanism. Lyko et al. (1998) suggested that the identified element participates in the long-range regulation of the imprinted 15q11-q13 domain or locally represses SNRPN expression from the maternal allele. </p><p>Schweizer et al. (1999) studied the mechanism by which small microdeletions within the 5-prime region of the SNRPN transcription unit affect the transcriptional activity and methylation status of distant imprinted genes throughout 15q11-q13 in cis. They analyzed the chromatin structure of the 150-kb SNRPN transcription unit for DNaseI- and MspI-hypersensitive sites. Using an in vivo approach on lymphoblastoid cell lines from PWS and AS individuals, they discovered that exon 1 of the SNRPN gene is flanked by prominent hypersensitive sites on the paternal allele, but is completely inaccessible to nucleases on the maternal allele. In contrast, they identified several regions of increased nuclease hypersensitivity on the maternal allele, one of which coincides with the minimal microdeletion region for AS, and another that lies in intron 1 immediately downstream of the paternal-specific hypersensitive sites. At several sites, parental origin-specific nuclease hypersensitivity was found to be correlated with hypermethylation on the allele contributed by the other parent. Schweizer et al. (1999) suggested that the differential parental origin-dependent chromatin conformations may govern access of regulatory protein complexes and/or RNAs that mediate interaction of the region with other genes. </p><p>Several observations had suggested that cis elements within the AS-SRO (shortest region of overlap) and PWS-SRO constitute an imprinting box that regulates the entire domain on both chromosomes. Shemer et al. (2000) showed that a minitransgene composed of 200-bp Snrpn promoter/exon 1 and a 1-kb sequence located approximately 35 kb upstream to the SNRPN promoter confer imprinting as judged by differential methylation, parent-of-origin-specific transcription, and asynchronous replication. </p><p>Geuns et al. (2003) studied the methylation patterns of the imprint control region of the SNRPN gene in human spermatozoa, oocytes at the germinal vesicle, metaphase I, and metaphase II stages, and preimplantation embryos. In spermatozoa, almost all potential methylation sites were unmethylated, whereas near-complete methylatation patterns were found in oocytes at all 3 developmental stages. In embryos, an average methylation pattern of 53% was found, indicating that the imprints, which had been set during gametogenesis, are stably maintained in the preimplantation embryo. Geuns et al. (2003) concluded that the maternal imprints for the imprint control region of the SNRPN gene are already reestablished at the germinal vesicle stage, and are not reestablished in a late oocyte stage or after fertilization, as had been previously reported. </p><p>Kantor et al. (2004) constructed a transgene including both the 4.3-kb PWS-SRO sequence and the 880-bp AS-SRO sequence and determined that the transgene carried out the entire imprinting process. The epigenetic features of this transgene resembled those previously observed on the endogenous locus, thus allowing analyses in mouse gametes and early embryos. In gametes, they identified a differentially methylated CpG cluster (DMR) on AS-SRO that was methylated in sperm and unmethylated in oocytes. This DMR specifically bound a maternal allele-discrimination protein that was involved in DMR maintenance through implantation when methylation of PWS-SRO the maternal allele takes place. While the AS-SRO was required in gametes to confer methylation on PWS-SRO, it was dispensable later in development. </p><p>The SNRPN 5-prime region colocalizes with the PWS imprinting center and contains 2 DNase I hypersensitive sites, DHS1 at the SNRPN promoter and DHS2 within intron 1, exclusively on the paternally inherited chromosome. Rodriguez-Jato et al. (2005) examined DHS1 and DHS2 to identify cis- and trans-acting regulatory elements within the endogenous SNRPN 5-prime region. Analysis of DHS1 by in vivo footprinting and chromatin immunoprecipitation identified allele-specific interactions with multiple regulatory proteins, including NRF1 (600879), which regulates genes involved in mitochondrial and metabolic functions. DHS2 acted as an enhancer of the SNRPN promoter and contained a highly conserved region that showed allele-specific interactions with unphosphorylated RNA polymerase II (see 180660), YY1 (600013), Sp1 (189906), and NRF1, further suggesting a key role for NRF1 in regulation of the SNRPN locus. </p><p>In mouse and humans, several alternative exons expressed from upstream alternative promoters of the Snrpn gene are expressed as IC transcripts (Bressler et al., 2001). However, there is no similarity between the nucleotide sequences of human and mouse IC transcripts. In mice, Mapendano et al. (2006) found strong expression of Snrpn IC transcripts in brain and ovary but not in other tissues. Expression levels in the brain were 7-fold higher compared to those in ovaries. In situ hybridization signals were observed in oocytes and granulosa cells of the secondary and developing follicles. Mapendano et al. (2006) suggested that the IC transcript may be associated with the establishment of PWS-IC methylation on the maternal chromosome as an AS-IC cis-acting element. </p>
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<strong>Cytogenetics</strong>
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<p>Sun et al. (1996) reported a patient with the PWS phenotype and a balanced reciprocal translocation t(15;19)(q12;q13.41), which was paternal in origin. By FISH analysis and examination of DNA by Southern blot hybridization, they found that the translocation breakpoint occurred between exons 0 and 1 of the SNRPN locus, outside of the SmN open reading frame. Sun et al. (1996) reported that the transcriptional activities of ZNF127 (MKRN3; 603856), IPW, PAR1 (600161), and PAR5 (600162) were detected with RT-PCR from fibroblasts of this patient, whereas transcription from only the first 2 exons and the last 7 exons of SNRPN was detected with RT-PCR. The complete SNRPN mRNA (10 exons) was not detected. Sun et al. (1996) suggested that the putative SNURF sequence would be interrupted in this patient, and this disruption may play a role in the etiology of the PWS phenotype. </p><p>Kuslich et al. (1999) likewise identified a de novo balanced translocation in a Prader-Willi syndrome patient: (4;15)(q27;q11.2)pat. The breakpoints lay between SNRPN exons 2 and 3. Parental-origin studies indicated that there was no uniparental disomy and no apparent deletion. The patient expressed ZNF127, SNRPN exons 1 and 2, IPW, and PAR1, but did not express either SNRPN exons 3 and 4 or PAR5, as assayed by RT-PCR, of peripheral blood cells. Kuslich et al. (1999) concluded that this patient and that reported by Sun et al. (1996) supported the contention that an intact genomic region and/or transcription of SNRPN exons 2 and 3 play a pivotal role in the manifestations of the major clinical phenotype in PWS. </p><p>Schulze et al. (1996) presented evidence suggesting that SNRPN is not a major determinant of the Prader-Willi syndrome. They mapped the breakpoint of balanced translocation (9;15)pat associated with most of the PWS features to a region between SNRPN and PAR1. Methylation and expression studies indicated that the paternal SNRPN allele was unaffected by the translocation, while IPW and PAR1 were unexpressed. This focused attention on genes distal to the breakpoint as the main candidate for PWS genes and was considered consistent with a cis action of the putative imprinting center (IC) gene located proximal to SNRPN (Sutcliffe et al., 1994; Buiting et al., 1995). Schulze et al. (1996) suggested that further studies of translocational disruption of the imprinted region may establish genotype/phenotype relationships in Prader-Willi syndrome, which they presumed to be a contiguous gene syndrome. </p><p>Balanced translocations affecting the paternal copy of 15q11-q13 have been proven to be a rare cause of Prader-Willi syndrome (PWS) or PWS-like features. Wirth et al. (2001) reported a de novo balanced reciprocal translocation, t(X;15)(q28;q12), in a female patient with atypical PWS. The translocation breakpoints in this patient and 2 previously reported patients mapped 70 to 80 kb distal to the SNURF-SNRPN gene and defined a breakpoint cluster region. The breakpoints disrupted one of several previously unknown 3-prime exons of this gene. RT-PCR experiments demonstrated that sequences distal to the breakpoint, including the C/D box snoRNA gene cluster HBII-85, as well as IPW and PAR1, were not expressed in the patient. The authors suggested that lack of expression of these sequences may contribute to the PWS phenotype. </p><p>Gallagher et al. (2002) suggested that the minimal critical region for PWS is approximately 121 kb within the SNRPN locus of more than 460 kb, bordered by a breakpoint cluster region identified in 3 individuals with PWS who had balanced reciprocal translocations and by the proximal deletion breakpoint of a familial deletion found in an unaffected mother, her 3 children with AS, and her father. The subset of SNRPN-encoded snoRNAs within this region comprises the PWCR1/HBII-85 (SNORD116-1; 605436) cluster of snoRNAs and the single HBII-438A snoRNA. These are the only known genes within this region, which suggests that loss of their expression may be responsible for much or all of the phenotype of PWS. This hypothesis is challenged by findings in 2 individuals with PWS who had balanced translocations with breakpoints upstream of the proposed minimal critical region but whose cells were reported to express transcripts within it, adjacent to these snoRNAs. By use of real-time quantitative RT-PCR, Gallagher et al. (2002) reassessed expression of these transcripts and of the snoRNAs themselves in fibroblasts of 1 of these patients. They found that the transcripts reported to be expressed in lymphoblast-somatic cell hybrids were not expressed in fibroblasts, and they suggested that the original results were misinterpreted. Most important, they showed that the PWCR1/HBII-85 snoRNAs were not expressed in fibroblasts of this individual. These results were consistent with the hypothesis that loss of expression of the snoRNAs in the proposed minimal critical region confers much or all of the phenotype of PWS. </p>
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<strong>Molecular Genetics</strong>
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<p>In 2 sibs with the typical phenotype of PWS but without a cytogenetically detectable deletion in 15q, Ishikawa et al. (1996) demonstrated deletion of SNRPN by fluorescence in situ hybridization. </p><p>Bielinska et al. (2000) reported a PWS family in which the father was mosaic for an imprinting center deletion on his paternal chromosome. The deletion chromosome had acquired a maternal methylation imprint in his somatic cells. Identical observations were made in chimeric mice generated from 2 independent embryonic stem cell lines harboring a similar deletion. Bielinska et al. (2000) concluded that the Prader-Willi syndrome imprinting center element is not only required for the establishment of the paternal imprint, but also for its postzygotic maintenance. </p>
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<p>The SNRPN promoter is embedded in a CpG island that is maternally methylated, is expressed only from the paternal chromosome, and lies within an imprinting center that is required for switching to and/or maintenance of the paternal epigenotype. In mice and humans, the SNRPN gene, as well as other loci in the region, are subject to genomic imprinting. Bressler et al. (2001) showed that a 0.9-kb deletion of exon 1 of mouse Snrpn did not disrupt imprinting or elicit any obvious phenotype, although it did allow the detection of previously unknown upstream exons. In contrast, a larger, overlapping 4.8-kb deletion caused a partial or mosaic imprinting defect and perinatal lethality when paternally inherited. </p><p>As part of studies of genomic imprinting in the Prader-Willi/Angelman domain, Tsai et al. (2002) inserted an agouti coat color cassette into the downstream open reading frame (ORF) of the Snurf-Snrpn locus in the mouse. The fusion gene was maternally silenced, as is Snurf-Snrpn, and produced a tan abdomen only when inherited paternally in otherwise black mice. A screen for dominant epigenetic or genetic events was performed with ENU mutagenesis, using a strategy whereby variation in abdominal color was scored at weaning. One mouse with maternal origin of the fusion gene had a tan abdomen and had an imprinting defect resulting in loss of both maternal methylation and silencing of the fusion gene. One mouse with paternal origin of the fusion gene was completely yellow and was found to have an ATG-to-AAG mutation in the initiation codon of the upstream ORF encoding Snurf. Northern blotting, immunoblotting, and transfection studies demonstrated that the mutation caused a 15-fold increase in translation of the downstream ORF in 2 fusion constructs, leading the authors to suggest that similar translational control may affect the normal Snurf-Snrpn transcript as well. </p><p>Peery et al. (2007) generated 2 deletions in mouse at a location analogous to that of the human AS-IC upstream of the SNRPN gene. Neither deletion produced an imprinting defect, suggesting that the location of the AS-IC is not strictly conserved between human and mouse. </p><p>Superovulation (ovarian stimulation) is an assisted reproductive technology (ART) for human subfertility/infertility treatment, which has been correlated with increased frequencies of imprinting disorders such as Angelman (105830) and Beckwith-Wiedemann syndromes (130650). Market-Velker et al. (2010) examined the effects of superovulation on genomic imprinting in individual mouse blastocyst stage embryos. Superovulation perturbed genomic imprinting of both maternally and paternally expressed genes. Loss of Snrpn, Peg3 (601483), and Kcnq1ot1 (604115) and gain of H19 (103280) imprinted methylation were observed. This perturbation was dose-dependent, with aberrant imprinted methylation more frequent at higher hormone dosage. Maternal as well as paternal H19 methylation was perturbed by superovulation. Market-Velker et al. (2010) postulated that superovulation may have dual effects during oogenesis, disrupting acquisition of imprints in growing oocytes, as well as maternal-effect gene products subsequently required for imprint maintenance during preimplantation development. </p>
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<div>
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<h4>
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Shemer, R., Hershko, A. Y., Perk, J., Mostoslavsky, R., Tsuberi, B., Cedar, H., Buiting, K., Razin, A.
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<strong>The imprinting box of the Prader-Willi/Angelman syndrome domain.</strong>
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Nature Genet. 26: 440-443, 2000.
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Sun, Y., Nicholls, R. D., Butler, M. G., Saitoh, S., Hainline, B. E., Palmer, C. G.
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<strong>Breakage in the SNRPN locus in a balanced 46,XY,t(15;19) Prader-Willi syndrome patient.</strong>
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Hum. Molec. Genet. 5: 517-524, 1996.
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Sutcliffe, J. S., Nakao, M., Christian, S., Orstavik, K. H., Tommerup, N., Ledbetter, D. H., Beaudet, A. L.
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<strong>Deletions of a differentially methylated CpG island at the SNRPN gene define a putative imprinting control region.</strong>
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Nature Genet. 8: 52-58, 1994.
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[PubMed: 7987392]
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Tsai, T.-F., Chen, K.-S., Weber, J. S., Justice, M. J., Beaudet, A. L.
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<strong>Evidence for translational regulation of the imprinted Snurf-Snrpn locus in mice.</strong>
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Hum. Molec. Genet. 11: 1659-1668, 2002.
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[PubMed: 12075010]
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Wawrzik, M., Spiess, A.-N., Herrmann, R., Buiting, K., Horsthemke, B.
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<strong>Expression of SNURF-SNRPN upstream transcripts and epigenetic regulatory genes during human spermatogenesis.</strong>
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[PubMed: 19471314]
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[Full Text: https://doi.org/10.1038/ejhg.2009.83]
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Wirth, J., Back, E., Huttenhofer, A., Nothwang, H.-G., Lich, C., Gross, S., Menzel, C,, Schinzel, A., Kioschis, P., Tommerup, N., Ropers, H.-H., Horsthemke, B., Buiting, K.
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<strong>A translocation breakpoint cluster disrupts the newly defined 3-prime end of the SNURF-SNRPN transcription unit on chromosome 15.</strong>
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Hum. Molec. Genet. 10: 201-210, 2001.
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[PubMed: 11159938]
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[Full Text: https://doi.org/10.1093/hmg/10.3.201]
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Patricia A. Hartz - updated : 3/10/2015<br>Patricia A. Hartz - updated : 8/15/2014<br>George E. Tiller - updated : 11/12/2010<br>Patricia A. Hartz - updated : 8/28/2009<br>Patricia A. Hartz - updated : 11/29/2007<br>George E. Tiller - updated : 5/30/2007<br>Matthew B. Gross - reorganized : 5/16/2006<br>Matthew B. Gross - updated : 5/16/2006<br>Cassandra L. Kniffin - updated : 4/28/2006<br>George E. Tiller - updated : 1/11/2006<br>George E. Tiller - updated : 6/2/2003<br>Victor A. McKusick - updated : 10/7/2002<br>Victor A. McKusick - updated : 6/25/2001<br>George E. Tiller - updated : 4/17/2001<br>Victor A. McKusick - updated : 7/26/2000<br>Ada Hamosh - updated : 4/28/2000<br>Victor A. McKusick - updated : 6/2/1999<br>Victor A. McKusick - updated : 5/14/1999<br>Victor A. McKusick - updated : 2/8/1999<br>Victor A. McKusick - updated : 3/5/1998<br>Moyra Smith - updated : 10/2/1996<br>Moyra Smith - updated : 5/14/1996
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Victor A. McKusick : 1/26/1993
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