An integrated map of structural variation in 2,504 human genomes

作者：Peter H. Sudmant, Tobias Rausch, Eugene J. Gardner, Robert E. Handsaker, Alexej S. Abyzov, John Huddleston, Yan Zhang, Kai Ye, Goo Jun, Markus Hsi-Yang Fritz, Miriam K. Konkel, Ankit Malhotra, Adrian M. Stütz, Xinghua Mindy Shi, Francesco Paolo Casale, Jieming Chen, Fereydoun Hormozdiari, Gargi Dayama, Ken Chen, Maika Malig, Mark Chaisson, Klaudia Walter, Sascha Meiers, Seva Kashin, Erik P. Garrison, Adam Auton, Hugo Y. K. Lam, Xinmeng Jasmine Mu, Can Alkan, Danny Antaki, Taejeong Bae, Eliza Cerveira, Peter S. Chines, Zechen Chong, Laura E. Clarke, Elif Dal, Li Ding, Sarah B. Emery, Xian Fan, Madhusudan Gujral, Fatma Kahveci, Jeffrey M. Kidd, Yu Kong, Eric-Wubbo Lameijer, Shane McCarthy, Paul Flicek, Richard A. Gibbs, Gábor Marth, Christopher E. Mason, Androniki Menelaou, Donna Marie Muzny, Bradley J. Nelson, Amina Noor, Nicholas F. Parrish, Matthew Pendleton, Andrew Quitadamo, Benjamin Raeder, Eric E. Schadt, Mallory Romanovitch, Andreas Schlattl, Robert Sebra, Andrey A. Shabalin, Andreas Untergasser, Jerilyn A. Walker, Min Wang, Fuli Yu, Chengsheng Zhang, Jing Zhang, Xiangqun Zheng-Bradley, Wanding Zhou, Thomas Zichner, Jonathan L. Sebat, Mark A. Batzer, Steven A. McCarroll, Ryan E. Mills, Mark Gerstein, Ali Kashif Bashir, Oliver Stegle, Scott E. Devine, Charles Lee, Evan E. Eichler, Jan O. Korbel · 发表于：Nature · 年份：2015 · DOI：10.1038/nature15394 · 被引用次数：2708 · 研究领域：Genetic Associations and Epidemiology、Genomic variations and chromosomal abnormalities、Genomics and Rare Diseases

Structural variants are implicated in numerous diseases and make up the majority of varying nucleotides among human genomes. Here we describe an integrated set of eight structural variant classes comprising both balanced and unbalanced variants, which we constructed using short-read DNA sequencing data and statistically phased onto haplotype blocks in 26 human populations. Analysing this set, we identify numerous gene-intersecting structural variants exhibiting population stratification and describe naturally occurring homozygous gene knockouts that suggest the dispensability of a variety of human genes. We demonstrate that structural variants are enriched on haplotypes identified by genome-wide association studies and exhibit enrichment for expression quantitative trait loci. Additionally, we uncover appreciable levels of structural variant complexity at different scales, including genic loci subject to clusters of repeated rearrangement and complex structural variants with multiple breakpoints likely to have formed through individual mutational events. Our catalogue will enhance future studies into structural variant demography, functional impact and disease association. The Structural Variation Analysis Group of The 1000 Genomes Project reports an integrated structural variation map based on discovery and genotyping of eight major structural variation classes in 2,504 unrelated individuals from across 26 populations; structural variation is compared within and between popu...