Document Detail


Disruption of a large intergenic noncoding RNA in subjects with neurodevelopmental disabilities.
MedLine Citation:
PMID:  23217328     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Michael E Talkowski; Gilles Maussion; Liam Crapper; Jill A Rosenfeld; Ian Blumenthal; Carrie Hanscom; Colby Chiang; Amelia Lindgren; Shahrin Pereira; Douglas Ruderfer; Alpha B Diallo; Juan Pablo Lopez; Gustavo Turecki; Elizabeth S Chen; Carolina Gigek; David J Harris; Va Lip; Yu An; Marta Biagioli; Marcy E Macdonald; Michael Lin; Stephen J Haggarty; Pamela Sklar; Shaun Purcell; Manolis Kellis; Stuart Schwartz; Lisa G Shaffer; Marvin R Natowicz; Yiping Shen; Cynthia C Morton; James F Gusella; Carl Ernst
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of human genetics     Volume:  91     ISSN:  1537-6605     ISO Abbreviation:  Am. J. Hum. Genet.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-14     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  0370475     Medline TA:  Am J Hum Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1128-34     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Affiliation:
Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Alternative Splicing
Base Sequence
Chromosome Breakpoints
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 2
Developmental Disabilities / genetics*
Female
Gene Order
Humans
Lymphocytes / metabolism
Molecular Sequence Data
Mutation*
Neural Stem Cells / metabolism
RNA, Long Untranslated / genetics*
Translocation, Genetic
Grant Support
ID/Acronym/Agency:
GM061354/GM/NIGMS NIH HHS; HD065286/HD/NICHD NIH HHS; K99MH095867/MH/NIMH NIH HHS; P01 GM061354/GM/NIGMS NIH HHS; R33MH087896/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Long Untranslated
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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