Increased exonic de novo mutation rate in individuals with schizophrenia

被引：298

作者：

Girard, Simon L. ^{[1
]}

Gauthier, Julie ^{[1
]}

Noreau, Anne ^{[1
]}

Xiong, Lan ^{[1
]}

Zhou, Sirui ^{[1
]}

Jouan, Loubna ^{[1
]}

Dionne-Laporte, Alexandre ^{[1
]}

Spiegelman, Dan ^{[1
]}

Henrion, Edouard ^{[1
]}

Diallo, Ousmane ^{[1
]}

Thibodeau, Pascale ^{[1
]}

Bachand, Isabelle ^{[2
]}

Bao, Jessie Y. J. ^{[3
]}

Tong, Amy Hin Yan ^{[3
]}

Lin, Chi-Ho ^{[3
]}

Millet, Bruno ^{[4
,5
]}

Jaafari, Nematollah ^{[4
,6
]}

Joober, Ridha ^{[7
]}

Dion, Patrick A. ^{[1
,8
]}

Lok, Si ^{[3
]}

Krebs, Marie-Odile ^{[4
,9
]}

Rouleau, Guy A. ^{[1
,2
,10
]}

机构：

[1] Univ Montreal, Ctr Excellence Neur, Ctr Hosp Univ Montreal Res Ctr, Montreal, PQ, Canada

[2] Univ Montreal, Ctr Excellence Neur, Ctr Hosp Univ St Justine Res Ctr, Montreal, PQ, Canada

[3] Univ Hong Kong, Li Ka Shing Fac Med, Genome Res Ctr, Hong Kong, Hong Kong, Peoples R China

[4] Univ Paris 05, INSERM, Lab Physiopathol Malad Psychiat, Ctr Psychiat & Neurosci UMR 894, Paris, France

[5] Univ Rennes 1, CH Guillaume Regnier Serv Hosp Univ Psychiat, Rennes, France

[6] Univ Poitiers, CHU, Ctr Hosp Henri Laborit, Unite Rech Clin Intersectorielle Psychiat,INSERM, Poitiers, France

[7] McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada

[8] Univ Montreal, Dept Pathol & Cellular Biol, Montreal, PQ, Canada

[9] Univ Paris 05, Fac Med Paris Descartes, Serv Hosp Univ, Ctr Hosp St Anne, Paris, France

[10] Univ Montreal, Dept Med, Fac Med, Montreal, PQ H3C 3J7, Canada

来源：

NATURE GENETICS | 2011年 / 43卷 / 09期

基金：

加拿大健康研究院;

关键词：

V(D)J RECOMBINATION; MENTAL-RETARDATION; COMMON VARIANTS; ASSOCIATION; SUBSTITUTIONS; DISEASE; GENE;

D O I：

10.1038/ng.886

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Schizophrenia is a severe psychiatric disorder that profoundly affects cognitive, behavioral and emotional processes. The wide spectrum of symptoms and clinical variability in schizophrenia suggest a complex genetic etiology, which is consistent with the numerous loci thus far identified by linkage, copy number variation and association studies(1-4). Although schizophrenia heritability may be as high as similar to 80%, the genes responsible for much of this heritability remain to be identified(5). Here we sequenced the exomes of 14 schizophrenia probands and their parents. We identified 15 de novo mutations (DNMs) in eight probands, which is significantly more than expected considering the previously reported DNM rate(6-8). In addition, 4 of the 15 identified DNMs are nonsense mutations, which is more than what is expected by chance(9). Our study supports the notion that DNMs may account for some of the heritability reported for schizophrenia while providing a list of genes possibly involved in disease pathogenesis.

引用

页码：860 / U65

页数：5

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