De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia

被引：323

作者：

Xu, Bin ^{[1
]}

Ionita-Laza, Juliana ^{[2
]}

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

Boone, Braden ^{[5
]}

Woodrick, Scarlet ^{[1
,6
]}

Sun, Yan ^{[1
]}

Levy, Shawn ^{[5
]}

Gogos, Joseph A. ^{[6
,7
]}

Karayiorgou, Maria ^{[1
]}

机构：

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

[2] Columbia Univ, Dept Biostat, New York, NY USA

[3] Weskoppies Hosp, Pretoria, South Africa

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

[5] HudsonAlpha Inst Biotechnol, Huntsville, AL USA

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

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

来源：

NATURE GENETICS | 2012年 / 44卷 / 12期

关键词：

ARCHITECTURE; PHENOTYPE; VARIANT;

D O I：

10.1038/ng.2446

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To evaluate evidence for de novo etiologies in schizophrenia, we sequenced at high coverage the exomes of families recruited from two populations with distinct demographic structures and history. We sequenced a total of 795 exomes from 231 parent-proband trios enriched for sporadic schizophrenia cases, as well as 34 unaffected trios. We observed in cases an excess of de novo nonsynonymous single-nucleotide variants as well as a higher prevalence of gene-disruptive de novo mutations relative to controls. We found four genes (LAMA2, DPYD, TRRAP and VPS39) affected by recurrent de novo events within or across the two populations, which is unlikely to have occurred by chance. We show that de novo mutations affect genes with diverse functions and developmental profiles, but we also find a substantial contribution of mutations in genes with higher expression in early fetal life. Our results help define the genomic and neural architecture of schizophrenia.

引用

页码：1365 / 1369

页数：5

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