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Mills, R.E.; Walter, K.; Stewart, C.; Handsaker, R.E.; Chen, K.; Alkan, C.; ... ; 1000 Genomes Project (2011)

Mapping copy number variation by population-scale genome sequencing

Article / Letter to editor
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...Show moreGenomic 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.Show less
structural variation segmental duplications short-read rearrangements disorders disease common schizophrenia polymorphism insertions
All authors
Mills, R.E.; Walter, K.; Stewart, C.; Handsaker, R.E.; Chen, K.; Alkan, C.; Abyzov, A.; Yoon, S.C.; Ye, K.; Cheetham, R.K.; Chinwalla, A.; Conrad, D.F.; Fu, Y.T.; Grubert, F.; Hajirasouliha, I.; Hormozdiari, F.; Iakoucheva, L.M.; Iqbal, Z.; Kang, S.L.; Kidd, J.M.; Konkel, M.K.; Korn, J.; Khurana, E.; Kural, D.; Lam, H.Y.K.; Leng, J.; Li, R.Q.; Li, Y.R.; Lin, C.Y.; Luo, R.B.; Mu, X.J.; Nemesh, J.; Peckham, H.E.; Rausch, T.; Scally, A.; Shi, X.H.; Stromberg, M.P.; Stutz, A.M.; Urban, A.E.; Walker, J.A.; Wu, J.T.; Zhang, Y.J.; Zhang, Z.D.D.; Batzer, M.A.; Ding, L.; Marth, G.T.; McVean, G.; Sebat, J.; Snyder, M.; Wang, J.; Eichler, E.E.; Gerstein, M.B.; Hurles, M.E.; Lee, C.; McCarroll, S.A.; Korbel, J.O.; 1000 Genomes Project
Date
2011-02-03
Journal
Nature
Volume
470
Issue
7332
Pages
59 - 65
DOI
doi:10.1038/nature09708