Mapping copy number variation by population-scale genome sequencing
Name
nihms-254846.pdf
Description
Accepted version
Size
652.35 KB
Format
Adobe PDF
Checksum (MD5)
f56c6d0512cd30e632d2b74127d0ffe3
Author(s)
Handsaker, Robert E.
Date Issued
August 2011
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Mills, Ryan E., et al., "Mapping copy number variation by population-scale genome sequencing." Nature 470 (2011): p. 59-65 doi 10.1038/nature09708 ©2011 Author(s)
Version
Author's final manuscript
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.
MIT Department
Broad Institute of MIT and Harvard
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/nature09708
