Exome sequencing supports a de novo mutational paradigm for schizophrenia

被引：333

作者：

Xu, Bin ^{[1
,2
]}

Roos, J. Louw ^{[3
,4
]}

Dexheimer, Phillip ^{[5
]}

Boone, Braden ^{[5
]}

Plummer, Brooks ^{[5
]}

Levy, Shawn ^{[5
]}

Gogos, Joseph A. ^{[2
,6
]}

Karayiorgou, Maria ^{[1
]}

机构：

[1] Columbia Univ, Dept Psychiat, New York, NY 10027 USA

[2] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY USA

[3] Univ Pretoria, Weskoppies Hosp, ZA-0002 Pretoria, South Africa

[4] Univ Pretoria, Dept Psychiat, ZA-0002 Pretoria, South Africa

[5] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

[6] Columbia Univ, Dept Neurosci, New York, NY USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 09期

关键词：

PROTEIN-COUPLED RECEPTORS; POPULATION; VARIANTS; DISEASE; FAMILIES; SPECTRUM; LINKAGE;

D O I：

10.1038/ng.902

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Despite its high heritability, a large fraction of individuals with schizophrenia do not have a family history of the disease (sporadic cases). Here we examined the possibility that rare de novo protein-altering mutations contribute to the genetic component of schizophrenia by sequencing the exomes of 53 sporadic cases, 22 unaffected controls and their parents. We identified 40 de novo mutations in 27 cases affecting 40 genes, including a potentially disruptive mutation in DGCR2, a gene located in the schizophrenia-predisposing 22q11.2 microdeletion region. A comparison to rare inherited variants indicated that the identified de novo mutations show a large excess of non-synonymous changes in schizophrenia cases, as well as a greater potential to affect protein structure and function. Our analyses suggest a major role for de novo mutations in schizophrenia as well as a large mutational target, which together provide a plausible explanation for the high global incidence and persistence of the disease.

引用

页码：864 / U72

页数：6

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