Disruption of a Large Intergenic Noncoding RNA in Subjects with Neurodevelopmental Disabilities

被引：52

作者：

Talkowski, Michael E. ^{[2
,3
,4
]}

Maussion, Gilles ^{[1
]}

Crapper, Liam ^{[1
]}

Rosenfeld, Jill A. ^{[5
]}

Blumenthal, Ian ^{[2
]}

Hanscom, Carrie ^{[2
]}

Chiang, Colby ^{[2
]}

Lindgren, Amelia ^{[6
,7
]}

Pereira, Shahrin ^{[6
,7
]}

Ruderfer, Douglas ^{[8
,9
]}

Diallo, Alpha B. ^{[1
]}

Lopez, Juan Pablo ^{[1
]}

Turecki, Gustavo ^{[1
]}

Chen, Elizabeth S. ^{[1
]}

Gigek, Carolina ^{[1
]}

Harris, David J. ^{[10
,11
]}

Lip, Va ^{[10
,11
]}

An, Yu ^{[10
,12
,13
]}

Biagioli, Marta ^{[2
,3
]}

MacDonald, Marcy E. ^{[2
,3
,4
]}

Lin, Michael ^{[4
,14
]}

Haggarty, Stephen J. ^{[2
,3
]}

Sklar, Pamela ^{[8
,9
]}

Purcell, Shaun ^{[2
,4
,8
,9
]}

Kellis, Manolis ^{[4
,14
]}

Schwartz, Stuart ^{[15
]}

Shaffer, Lisa G. ^{[5
]}

Natowicz, Marvin R. ^{[16
,17
,19
]}

Shen, Yiping ^{[2
,10
,11
,18
]}

Morton, Cynthia C. ^{[4
,6
,7
]}

Gusella, James F. ^{[3
,4
]}

Ernst, Carl ^{[1
,2
]}

机构：

[1] McGill Univ, Douglas Hosp, Res Inst, Dept Psychiat, Quebec City, ON H4H 1R3, Canada

[2] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[3] Harvard Univ, Dept Neurol & Genet, Boston, MA 02114 USA

[4] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02114 USA

[5] Signature Genom Inc, PerkinElmer, Spokane, WA 99207 USA

[6] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[8] Mt Sinai Sch Med, Dept Psychiat & Genet, New York, NY 10029 USA

[9] Mt Sinai Sch Med, Dept Genom Sci, New York, NY 10029 USA

[10] Harvard Univ, Sch Med, Dept Lab Med, Boston Childrens Hosp, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[12] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China

[13] Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China

[14] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02114 USA

[15] Genzyme Genet Inc, Labcorp, Res Triangle Pk, NC 27709 USA

[16] Cleveland Clin, Inst Pathol & Lab Med, Cleveland, OH 44195 USA

[17] Cleveland Clin, Inst Genom Med, Cleveland, OH 44195 USA

[18] Shanghai Jiao Tong Univ, Sch Med, Shanghai Childrens Med Ctr, Shanghai 200127, Peoples R China

[19] Cleveland Clin, Inst Neurol & Pediat, Cleveland, OH 44195 USA

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2012年 / 91卷 / 06期

基金：

美国国家科学基金会;

关键词：

GENE-EXPRESSION; CHROMATIN; REARRANGEMENTS; REVEALS; GENOME;

D O I：

10.1016/j.ajhg.2012.10.016

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1128 / 1134

页数：7

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