Mapping copy number variation by population-scale genome sequencing

Ryan E. Mills, Klaudia Walter, Chip Stewart, Robert E. Handsaker, Ken Chen, Can Alkan, Alexej Abyzov, Seungtai Chris Yoon, Kai Ye, R. Keira Cheetham, Asif Chinwalla, Donald F. Conrad, Yutao Fu, Fabian Grubert, Iman Hajirasouliha, Fereydoun Hormozdiari, Lilia M. Iakoucheva, Zamin Iqbal, Shuli Kang, Jeffrey M. KiddMiriam K. Konkel, Joshua Korn, Ekta Khurana, Deniz Kural, Hugo Y.K. Lam, Jing Leng, Ruiqiang Li, Yingrui Li, Chang Yun Lin, Ruibang Luo, Xinmeng Jasmine Mu, James Nemesh, Heather E. Peckham, Tobias Rausch, Aylwyn Scally, Xinghua Shi, Michael P. Stromberg, Adrian M. Sütz, Alexander Eckehart Urban, Jerilyn A. Walker, Jiantao Wu, Yujun Zhang, Zhengdong D. Zhang, Mark A. Batzer, Li Ding, Gabor T. Marth, Gil McVean, Jonathan Sebat, Michael Snyder, Jun Wang, Kenny Ye, Evan E. Eichler, Mark B. Gerstein, Matthew E. Hurles, Charles Lee, Steven A. McCarroll, Jan O. Korbel, Francis S. Collins

Research output: Contribution to journalArticlepeer-review

760 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)59-65
Number of pages7
Issue number7332
StatePublished - Feb 3 2011
Externally publishedYes

ASJC Scopus subject areas

  • General


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