Origins and functional impact of copy number variation in the human genome

被引：1369

作者：

Conrad, Donald F. ^{[1
]}

Pinto, Dalila ^{[2
,3
]}

Redon, Richard ^{[1
,4
]}

Feuk, Lars ^{[2
,3
,5
]}

Gokcumen, Omer ^{[6
,7
]}

Zhang, Yujun ^{[1
]}

Aerts, Jan ^{[1
]}

Andrews, T. Daniel ^{[1
]}

Barnes, Chris ^{[1
]}

Campbell, Peter ^{[1
]}

Fitzgerald, Tomas ^{[1
]}

Hu, Min ^{[1
]}

Ihm, Chun Hwa ^{[6
,7
]}

Kristiansson, Kati ^{[1
]}

MacArthur, Daniel G. ^{[1
]}

MacDonald, Jeffrey R. ^{[2
,3
]}

Onyiah, Ifejinelo ^{[1
]}

Pang, Andy Wing Chun ^{[2
,3
]}

Robson, Sam ^{[1
]}

Stirrups, Kathy ^{[1
]}

Valsesia, Armand ^{[1
]}

Walter, Klaudia ^{[1
]}

Wei, John ^{[2
,3
]}

Tyler-Smith, Chris ^{[1
]}

Carter, Nigel P. ^{[1
]}

Lee, Charles ^{[6
,7
]}

Scherer, Stephen W. ^{[2
,3
,8
]}

Hurles, Matthew E. ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

[2] Hosp Sick Children, Ctr Appl Genom, MaRS Ctr, Toronto, ON M5G 1L7, Canada

[3] Hosp Sick Children, Program Genet & Genom, MaRS Ctr, Toronto, ON M5G 1L7, Canada

[4] INSERM, UMR915, Inst Thorax, F-44035 Nantes, France

[5] Uppsala Univ, Rudbeck Lab, Uppsala Dept Genet & Pathol, S-75185 Uppsala, Sweden

[6] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA 02115 USA

[8] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

来源：

NATURE | 2010年 / 464卷 / 7289期

基金：

英国惠康基金; 加拿大健康研究院; 美国国家卫生研究院; 芬兰科学院;

关键词：

RECOMBINATION HOT-SPOTS; STRUCTURAL VARIATION; POSITIVE SELECTION; DELETION POLYMORPHISM; WIDE ASSOCIATION; GENE; REARRANGEMENTS; INSTABILITY; NUCLEOTIDE; EXPRESSION;

D O I：

10.1038/nature08516

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.

引用

页码：704 / 712

页数：9

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