Mapping copy number variation by population-scale genome sequencing.

Nature
Authors
Keywords
Abstract

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.

Year of Publication
2011
Journal
Nature
Volume
470
Issue
7332
Pages
59-65
Date Published
2011 Feb 03
ISSN
1476-4687
DOI
10.1038/nature09708
PubMed ID
21293372
PubMed Central ID
PMC3077050
Links
Grant list
077009 / Wellcome Trust / United Kingdom
R01 GM081533-01A1 / GM / NIGMS NIH HHS / United States
077192 / Wellcome Trust / United Kingdom
R01 HG004719-01 / HG / NHGRI NIH HHS / United States
R01 HG004719 / HG / NHGRI NIH HHS / United States
R01 HG004719-04 / HG / NHGRI NIH HHS / United States
G1000758 / Medical Research Council / United Kingdom
U01 HG005209-02 / HG / NHGRI NIH HHS / United States
RC2 HG005552 / HG / NHGRI NIH HHS / United States
G0701805 / Medical Research Council / United Kingdom
U01 HG005209-01 / HG / NHGRI NIH HHS / United States
P41 HG004221-03S2 / HG / NHGRI NIH HHS / United States
R01 MH091350 / MH / NIMH NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 GM081533-04 / GM / NIGMS NIH HHS / United States
RC2 HG005552-01 / RC / CCR NIH HHS / United States
P41 HG004221-03S3 / HG / NHGRI NIH HHS / United States
P41 HG004221-02 / HG / NHGRI NIH HHS / United States
R01 GM059290 / GM / NIGMS NIH HHS / United States
R01 GM081533-03 / GM / NIGMS NIH HHS / United States
R01 GM081533 / GM / NIGMS NIH HHS / United States
RC2 HG005552-02 / HG / NHGRI NIH HHS / United States
077014 / Wellcome Trust / United Kingdom
R01 HG004719-02 / HG / NHGRI NIH HHS / United States
P41 HG004221-01 / HG / NHGRI NIH HHS / United States
062023 / Wellcome Trust / United Kingdom
P41 HG004221-03S1 / HG / NHGRI NIH HHS / United States
P41 HG004221-03 / HG / NHGRI NIH HHS / United States
085532 / Wellcome Trust / United Kingdom
R01 HG004719-02S1 / HG / NHGRI NIH HHS / United States
R01 HG004719-03 / HG / NHGRI NIH HHS / United States
U01 HG005209 / HG / NHGRI NIH HHS / United States
R21 AA022707 / AA / NIAAA NIH HHS / United States
P41 HG004221 / HG / NHGRI NIH HHS / United States
R01 GM081533-02 / GM / NIGMS NIH HHS / United States