Mapping copy number variation by population-scale genome sequencing

被引：820

作者：

Mills, Ryan E. ^{[2
,3
]}

Walter, Klaudia ^{[4
]}

Stewart, Chip ^{[5
]}

Handsaker, Robert E. ^{[6
,7
]}

Chen, Ken ^{[8
]}

Alkan, Can ^{[9
,10
]}

Abyzov, Alexej ^{[11
]}

Yoon, Seungtai Chris ^{[12
,13
]}

Ye, Kai ^{[14
,15
]}

Cheetham, R. Keira ^{[16
]}

Chinwalla, Asif ^{[8
]}

Conrad, Donald F. ^{[4
]}

Fu, Yutao ^{[17
]}

Grubert, Fabian ^{[18
]}

Hajirasouliha, Iman ^{[19
]}

Hormozdiari, Fereydoun ^{[19
]}

Iakoucheva, Lilia M. ^{[20
]}

Iqbal, Zamin ^{[21
]}

Kang, Shuli ^{[20
]}

Kidd, Jeffrey M. ^{[9
]}

Konkel, Miriam K. ^{[22
]}

Korn, Joshua ^{[6
,7
]}

Khurana, Ekta ^{[11
,23
]}

Kural, Deniz ^{[5
]}

Lam, Hugo Y. K. ^{[18
]}

Leng, Jing ^{[11
]}

Li, Ruiqiang ^{[24
]}

Li, Yingrui ^{[24
]}

Lin, Chang-Yun ^{[25
]}

Luo, Ruibang ^{[24
]}

Mu, Xinmeng Jasmine ^{[11
]}

Nemesh, James ^{[6
,7
]}

Peckham, Heather E. ^{[17
]}

Rausch, Tobias ^{[1
]}

Scally, Aylwyn ^{[4
]}

Shi, Xinghua ^{[2
,3
]}

Stromberg, Michael P. ^{[5
]}

Stuetz, Adrian M. ^{[1
]}

Urban, Alexander Eckehart ^{[18
,31
]}

Walker, Jerilyn A. ^{[22
]}

Wu, Jiantao ^{[5
]}

Zhang, Yujun ^{[4
]}

Zhang, Zhengdong D. ^{[11
]}

Batzer, Mark A. ^{[22
]}

Ding, Li ^{[8
,26
]}

Marth, Gabor T. ^{[5
]}

McVean, Gil ^{[27
]}

Sebat, Jonathan ^{[20
]}

Snyder, Michael ^{[18
]}

Wang, Jun ^{[24
,28
]}

机构：

[1] European Mol Biol Lab, Genome Biol Res Unit, Heidelberg, Germany

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

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, England

[5] Boston Coll, Dept Biol, Boston, MA USA

[6] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA

[7] MIT, Cambridge, MA 02139 USA

[8] Washington Univ, Genome Ctr, St Louis, MO USA

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

[10] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

[11] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA

[12] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY USA

[13] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA

[14] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands

[15] Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands

[16] Illumina Cambridge Ltd, Saffron Walden CB10 1XL, Essex, England

[17] Life Technol, Beverly, MA USA

[18] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

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

[20] Univ Calif San Diego, Inst Genom Med, Dept Cellular & Mol Med, Dept Psychiat, La Jolla, CA 92093 USA

[21] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[22] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA

[23] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA

[24] BGI Shenzhen, Shenzhen 518083, Peoples R China

[25] Albert Einstein Coll Med, Bronx, NY 10467 USA

[26] Washington Univ, Dept Genet, St Louis, MO 63110 USA

[27] Univ Oxford, Dept Stat, Oxford OX3 7BN, England

[28] Univ Copenhagen, Dept Biol, Copenhagen, Denmark

[29] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA

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

[31] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA

来源：

NATURE | 2011年 / 470卷 / 7332期

基金：

美国国家卫生研究院; 中国国家自然科学基金;

关键词：

STRUCTURAL VARIATION; SEGMENTAL DUPLICATIONS; SHORT-READ; REARRANGEMENTS; COMMON; POLYMORPHISM; INSERTIONS; DELETIONS; SNPS;

D O I：

10.1038/nature09708

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：

Genomic structural variants (SVs) are abundant in humans, differing from other forms of variation in extent, origin and functional impact. Despite progress in SV characterization, the nucleotide resolution architecture of most SVs remains unknown. We constructed a map of unbalanced SVs (that is, copy number variants) based on whole genome DNA sequencing data from 185 human genomes, integrating evidence from complementary SV discovery approaches with extensive experimental validations. Our map encompassed 22,025 deletions and 6,000 additional SVs, including insertions and tandem duplications. Most SVs (53%) were mapped to nucleotide resolution, which facilitated analysing their origin and functional impact. We examined numerous whole and partial gene deletions with a genotyping approach and observed a depletion of gene disruptions amongst high frequency deletions. Furthermore, we observed differences in the size spectra of SVs originating from distinct formation mechanisms, and constructed a map of SV hotspots formed by common mechanisms. Our analytical framework and SV map serves as a resource for sequencing-based association studies.

引用

页码：59 / 65

页数：7

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