Discovery and genotyping of genome structural polymorphism by sequencing on a population scale

被引：239

作者：

Handsaker, Robert E. ^{[1
,2
]}

Korn, Joshua M. ^{[1
,2
]}

Nemesh, James ^{[1
,2
]}

McCarroll, Steven A. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

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

[3] Stanley Ctr Psychiat Dis Res, Cambridge, MA USA

来源：

NATURE GENETICS | 2011年 / 43卷 / 03期

关键词：

COPY-NUMBER; IMPUTATION; VARIANTS; MAP; SNPS;

D O I：

10.1038/ng.768

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Accurate and complete analysis of genome variation in large populations will be required to understand the role of genome variation in complex disease. We present an analytical framework for characterizing genome deletion polymorphism in populations using sequence data that are distributed across hundreds or thousands of genomes. Our approach uses population-level concepts to reinterpret the technical features of sequence data that often reflect structural variation. In the 1000 Genomes Project pilot, this approach identified deletion polymorphism across 168 genomes (sequenced at 4x average coverage) with sensitivity and specificity unmatched by other algorithms. We also describe a way to determine the allelic state or genotype of each deletion polymorphism in each genome; the 1000 Genomes Project used this approach to type 13,826 deletion polymorphisms (48-995,664 bp) at high accuracy in populations. These methods offer a way to relate genome structural polymorphism to complex disease in populations.

引用

页码：269 / U126

页数：10

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