Disruption of a Large Intergenic Noncoding RNA in Subjects with Neurodevelopmental Disabilities
Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant c...
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| Veröffentlicht in: | American journal of human genetics 2012-12, Vol.91 (6), p.1128-1134 |
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| creator | Talkowski, Michael E. Maussion, Gilles Crapper, Liam Rosenfeld, Jill A. Blumenthal, Ian Hanscom, Carrie Chiang, Colby Lindgren, Amelia Pereira, Shahrin Ruderfer, Douglas Diallo, Alpha B. Lopez, Juan Pablo Turecki, Gustavo Chen, Elizabeth S. Gigek, Carolina Harris, David J. Lip, Va An, Yu Biagioli, Marta MacDonald, Marcy E. Lin, Michael Haggarty, Stephen J. Sklar, Pamela Purcell, Shaun Kellis, Manolis Schwartz, Stuart Shaffer, Lisa G. Natowicz, Marvin R. Shen, Yiping Morton, Cynthia C. Gusella, James F. Ernst, Carl |
| description | Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders. |
| doi_str_mv | 10.1016/j.ajhg.2012.10.016 |
| format | Article |
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We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1016/j.ajhg.2012.10.016</identifier><identifier>PMID: 23217328</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Cambridge, MA: Elsevier Inc</publisher><subject>Adolescent ; Alternative Splicing ; Base Sequence ; Biological and medical sciences ; Brain ; Chromosome Breakpoints ; Chromosomes ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 2 ; Developmental disabilities ; Developmental Disabilities - genetics ; Diagnostic tests ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Order ; Genetics of eukaryotes. Biological and molecular evolution ; Humans ; Lymphocytes - metabolism ; Medical genetics ; Medical sciences ; Molecular and cellular biology ; Molecular Sequence Data ; Mutation ; Neural Stem Cells - metabolism ; Neurological disorders ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - genetics ; Translocation, Genetic</subject><ispartof>American journal of human genetics, 2012-12, Vol.91 (6), p.1128-1134</ispartof><rights>2012 The American Society of Human Genetics</rights><rights>2014 INIST-CNRS</rights><rights>Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Cell Press Dec 7, 2012</rights><rights>2012 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved. 2012 The American Society of Human Genetics</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c546t-839c9965ec6649c6e8bd9f6bae4475d75da39c598ca7161da97578bb0f4a8e333</citedby><cites>FETCH-LOGICAL-c546t-839c9965ec6649c6e8bd9f6bae4475d75da39c598ca7161da97578bb0f4a8e333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3516594/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002929712005757$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,3537,27901,27902,53766,53768,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26711367$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23217328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Talkowski, Michael E.</creatorcontrib><creatorcontrib>Maussion, Gilles</creatorcontrib><creatorcontrib>Crapper, Liam</creatorcontrib><creatorcontrib>Rosenfeld, Jill A.</creatorcontrib><creatorcontrib>Blumenthal, Ian</creatorcontrib><creatorcontrib>Hanscom, Carrie</creatorcontrib><creatorcontrib>Chiang, Colby</creatorcontrib><creatorcontrib>Lindgren, Amelia</creatorcontrib><creatorcontrib>Pereira, Shahrin</creatorcontrib><creatorcontrib>Ruderfer, Douglas</creatorcontrib><creatorcontrib>Diallo, Alpha B.</creatorcontrib><creatorcontrib>Lopez, Juan Pablo</creatorcontrib><creatorcontrib>Turecki, Gustavo</creatorcontrib><creatorcontrib>Chen, Elizabeth S.</creatorcontrib><creatorcontrib>Gigek, Carolina</creatorcontrib><creatorcontrib>Harris, David J.</creatorcontrib><creatorcontrib>Lip, Va</creatorcontrib><creatorcontrib>An, Yu</creatorcontrib><creatorcontrib>Biagioli, Marta</creatorcontrib><creatorcontrib>MacDonald, Marcy E.</creatorcontrib><creatorcontrib>Lin, Michael</creatorcontrib><creatorcontrib>Haggarty, Stephen J.</creatorcontrib><creatorcontrib>Sklar, Pamela</creatorcontrib><creatorcontrib>Purcell, Shaun</creatorcontrib><creatorcontrib>Kellis, Manolis</creatorcontrib><creatorcontrib>Schwartz, Stuart</creatorcontrib><creatorcontrib>Shaffer, Lisa G.</creatorcontrib><creatorcontrib>Natowicz, Marvin R.</creatorcontrib><creatorcontrib>Shen, Yiping</creatorcontrib><creatorcontrib>Morton, Cynthia C.</creatorcontrib><creatorcontrib>Gusella, James F.</creatorcontrib><creatorcontrib>Ernst, Carl</creatorcontrib><title>Disruption of a Large Intergenic Noncoding RNA in Subjects with Neurodevelopmental Disabilities</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>Large intergenic noncoding (linc) RNAs represent a newly described class of ribonucleic acid whose importance in human disease remains undefined. We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. Together, these subjects with disruption of LINC00299 implicate this particular noncoding RNA in brain development and raise the possibility that, as a class, abnormalities of lincRNAs may play a significant role in human developmental disorders.</description><subject>Adolescent</subject><subject>Alternative Splicing</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Brain</subject><subject>Chromosome Breakpoints</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 11</subject><subject>Chromosomes, Human, Pair 2</subject><subject>Developmental disabilities</subject><subject>Developmental Disabilities - genetics</subject><subject>Diagnostic tests</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Order</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Humans</subject><subject>Lymphocytes - metabolism</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Neural Stem Cells - metabolism</subject><subject>Neurological disorders</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Translocation, Genetic</subject><issn>0002-9297</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVuLFDEQhRtR3HH1D_ggARF8mTGXzg1EWNbbwjCCl-eQTlfPpOlJZpPuEf-9aWZcLw9CoODkq0NVnap6SvCKYCJe9Svb77YrigktwqpI96oF4UwuhcD8frXAGNOlplpeVI9y7jEmRGH2sLqgjBLJqFpU5q3PaTqMPgYUO2TR2qYtoJswQqnBO7SJwcXWhy36vLlCPqAvU9ODGzP67scd2sCUYgtHGOJhD2G0AyqWtvGDHz3kx9WDzg4ZnpzrZfXt_buv1x-X608fbq6v1kvHazEuFdNOa8HBCVFrJ0A1re5EY6GuJW_Ls4XgWjkriSCt1ZJL1TS4q60Cxthl9ebke5iaPbSuTJLsYA7J7236YaL15u-f4HdmG4-GcSK4rovBy7NBircT5NHsfXYwDDZAnLIhVFJZY6J4QZ__g_ZxSqGsVyimytEVnil6olyKOSfo7oYh2Mz5md7M-Zk5v1krUml69ucady2_AivAizNgs7NDl2xwPv_mhCSECVm41ycOytGPHpLJzkNw0PpUwjNt9P-b4ydiGrmr</recordid><startdate>20121207</startdate><enddate>20121207</enddate><creator>Talkowski, Michael E.</creator><creator>Maussion, Gilles</creator><creator>Crapper, Liam</creator><creator>Rosenfeld, Jill A.</creator><creator>Blumenthal, Ian</creator><creator>Hanscom, Carrie</creator><creator>Chiang, Colby</creator><creator>Lindgren, Amelia</creator><creator>Pereira, Shahrin</creator><creator>Ruderfer, Douglas</creator><creator>Diallo, Alpha B.</creator><creator>Lopez, Juan Pablo</creator><creator>Turecki, Gustavo</creator><creator>Chen, Elizabeth S.</creator><creator>Gigek, Carolina</creator><creator>Harris, David J.</creator><creator>Lip, Va</creator><creator>An, Yu</creator><creator>Biagioli, Marta</creator><creator>MacDonald, Marcy E.</creator><creator>Lin, Michael</creator><creator>Haggarty, Stephen J.</creator><creator>Sklar, Pamela</creator><creator>Purcell, Shaun</creator><creator>Kellis, Manolis</creator><creator>Schwartz, Stuart</creator><creator>Shaffer, Lisa G.</creator><creator>Natowicz, Marvin R.</creator><creator>Shen, Yiping</creator><creator>Morton, Cynthia C.</creator><creator>Gusella, James F.</creator><creator>Ernst, Carl</creator><general>Elsevier Inc</general><general>Cell Press</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20121207</creationdate><title>Disruption of a Large Intergenic Noncoding RNA in Subjects with Neurodevelopmental Disabilities</title><author>Talkowski, Michael E. ; Maussion, Gilles ; Crapper, Liam ; Rosenfeld, Jill A. ; Blumenthal, Ian ; Hanscom, Carrie ; Chiang, Colby ; Lindgren, Amelia ; Pereira, Shahrin ; Ruderfer, Douglas ; Diallo, Alpha B. ; Lopez, Juan Pablo ; Turecki, Gustavo ; Chen, Elizabeth S. ; Gigek, Carolina ; Harris, David J. ; Lip, Va ; An, Yu ; Biagioli, Marta ; MacDonald, Marcy E. ; Lin, Michael ; Haggarty, Stephen J. ; Sklar, Pamela ; Purcell, Shaun ; Kellis, Manolis ; Schwartz, Stuart ; Shaffer, Lisa G. ; Natowicz, Marvin R. ; Shen, Yiping ; Morton, Cynthia C. ; Gusella, James F. ; Ernst, Carl</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c546t-839c9965ec6649c6e8bd9f6bae4475d75da39c598ca7161da97578bb0f4a8e333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adolescent</topic><topic>Alternative Splicing</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Brain</topic><topic>Chromosome Breakpoints</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 11</topic><topic>Chromosomes, Human, Pair 2</topic><topic>Developmental disabilities</topic><topic>Developmental Disabilities - genetics</topic><topic>Diagnostic tests</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Order</topic><topic>Genetics of eukaryotes. 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We identified a severely developmentally delayed 16-year-old female with karyotype 46,XX,t(2;11)(p25.1;p15.1)dn in the absence of clinically significant copy number variants (CNVs). DNA capture followed by next-generation sequencing of the translocation breakpoints revealed disruption of a single noncoding gene on chromosome 2, LINC00299, whose RNA product is expressed in all tissues measured, but most abundantly in brain. Among a series of additional, unrelated subjects referred for clinical diagnostic testing who showed CNV affecting this locus, we identified four with exon-crossing deletions in association with neurodevelopmental abnormalities. No disruption of the LINC00299 coding sequence was seen in almost 14,000 control subjects. 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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adolescent Alternative Splicing Base Sequence Biological and medical sciences Brain Chromosome Breakpoints Chromosomes Chromosomes, Human, Pair 11 Chromosomes, Human, Pair 2 Developmental disabilities Developmental Disabilities - genetics Diagnostic tests Female Fundamental and applied biological sciences. Psychology Gene Order Genetics of eukaryotes. Biological and molecular evolution Humans Lymphocytes - metabolism Medical genetics Medical sciences Molecular and cellular biology Molecular Sequence Data Mutation Neural Stem Cells - metabolism Neurological disorders Ribonucleic acid RNA RNA, Long Noncoding - genetics Translocation, Genetic |
| title | Disruption of a Large Intergenic Noncoding RNA in Subjects with Neurodevelopmental Disabilities |
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