Personalized copy number and segmental duplication maps using next-generation sequencing

被引：513

作者：

Alkan, Can ^{[1
,2
]}

Kidd, Jeffrey M. ^{[1
]}

Marques-Bonet, Tomas ^{[1
,3
]}

Aksay, Gozde ^{[1
]}

Antonacci, Francesca ^{[1
]}

Hormozdiari, Fereydoun ^{[4
]}

Kitzman, Jacob O. ^{[1
]}

Baker, Carl ^{[1
]}

Malig, Maika ^{[1
]}

Mutlu, Onur ^{[5
]}

Sahinalp, S. Cenk ^{[4
]}

Gibbs, Richard A. ^{[6
]}

Eichler, Evan E. ^{[1
,2
]}

机构：

[1] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA

[2] Howard Hughes Med Inst, Seattle, WA USA

[3] UPF, CSIC, Inst Biol Evolut, Barcelona, Catalonia, Spain

[4] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada

[5] Carnegie Mellon Univ, Dept Elect & Comp Engn, Pittsburgh, PA 15213 USA

[6] Baylor Coll Med, Houston, TX 77030 USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 10期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

LARGE-SCALE VARIATION; HUMAN-GENOME; STRUCTURAL VARIATION; SUSCEPTIBILITY; POLYMORPHISMS; HYBRIDIZATION; PREDISPOSES; REGIONS; SNPS;

D O I：

10.1038/ng.437

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Despite their importance in gene innovation and phenotypic variation, duplicated regions have remained largely intractable owing to difficulties in accurately resolving their structure, copy number and sequence content. We present an algorithm (mrFAST) to comprehensively map next-generation sequence reads, which allows for the prediction of absolute copy-number variation of duplicated segments and genes. We examine three human genomes and experimentally validate genome-wide copy number differences. We estimate that, on average, 73-87 genes vary in copy number between any two individuals and find that these genic differences overwhelmingly correspond to segmental duplications (odds ratio = 135; P < 2.2 x 10(-16)). Our method can distinguish between different copies of highly identical genes, providing a more accurate assessment of gene content and insight into functional constraint without the limitations of array-based technology.

引用

页码：1061 / U29

页数：8

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