Integrated detection and population-genetic analysis of SNPs and copy number variation

被引：683

作者：

McCarroll, Steven A. ^{[1
,2
,3
,4
,5
]}

Kuruvilla, Finny G. ^{[1
,2
,3
,4
,5
]}

Korn, Joshua M. ^{[1
,2
,3
,4
,6
,7
]}

Cawley, Simon ^{[8
]}

Nemesh, James ^{[1
,2
]}

Wysoker, Alec ^{[1
,2
]}

Shapero, Michael H. ^{[8
]}

de Bakker, Paul I. W. ^{[1
,2
,5
,9
,10
]}

Maller, Julian B. ^{[4
]}

Kirby, Andrew ^{[4
]}

Elliott, Amanda L. ^{[1
,2
]}

Parkin, Melissa ^{[1
,2
]}

Hubbell, Earl ^{[8
]}

Webster, Teresa ^{[8
]}

Mei, Rui ^{[8
]}

Veitch, James ^{[8
]}

Collins, Patrick J. ^{[8
]}

Handsaker, Robert ^{[1
,2
]}

Lincoln, Steve ^{[8
]}

Nizzari, Marcia ^{[1
,2
]}

Blume, John ^{[8
]}

Jones, Keith W. ^{[8
]}

Rava, Rich ^{[8
]}

Daly, Mark J. ^{[1
,2
,4
,5
,11
]}

Gabriel, Stacey B. ^{[1
,2
]}

Altshuler, David ^{[1
,2
,3
,4
,5
,11
]}

机构：

[1] MIT, Broad Inst, Program Med & Populat Genet & Genet Anal Platform, Cambridge, MA 02142 USA

[2] Harvard Univ, Cambridge, MA 02142 USA

[3] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[4] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

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

[6] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[7] Harvard Univ, Grad Program Biophys, Cambridge, MA 02138 USA

[8] Affymetrix Inc, Santa Clara, CA 95051 USA

[9] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Partners HealthCare Syst Ctr Genet & Genom, Boston, MA 02115 USA

[11] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 10期

关键词：

D O I：

10.1038/ng.238

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Dissecting the genetic basis of disease risk requires measuring all forms of genetic variation, including SNPs and copy number variants (CNVs), and is enabled by accurate maps of their locations, frequencies and population-genetic properties. We designed a hybrid genotyping array (Affymetrix SNP 6.0) to simultaneously measure 906,600 SNPs and copy number at 1.8 million genomic locations. By characterizing 270 HapMap samples, we developed a map of human CNV (at 2-kb breakpoint resolution) informed by integer genotypes for 1,320 copy number polymorphisms (CNPs) that segregate at an allele frequency >1%. More than 80% of the sequence in previously reported CNV regions fell outside our estimated CNV boundaries, indicating that large (>100 kb) CNVs affect much less of the genome than initially reported. Approximately 80% of observed copy number differences between pairs of individuals were due to common CNPs with an allele frequency >5%, and more than 99% derived from inheritance rather than new mutation. Most common, diallelic CNPs were in strong linkage disequilibrium with SNPs, and most low-frequency CNVs segregated on specific SNP haplotypes.

引用

页码：1166 / 1174

页数：9

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