Title

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

Authors

Peter H. Sudmant, University of Washington, Seattle
Tobias Rausch, European Molecular Biology Laboratory Heidelberg
Eugene J. Gardner, University of Maryland School of Medicine
Robert E. Handsaker, Harvard Medical School
Alexej Abyzov, Mayo Clinic
John Huddleston, University of Washington, Seattle
Yan Zhang, Yale University
Kai Ye, Washington University School of Medicine in St. Louis
Goo Jun, University of Michigan, Ann Arbor
Markus His Yang Fritz, European Molecular Biology Laboratory Heidelberg
Miriam K. Konkel, Louisiana State University
Ankit Malhotra, Jackson Laboratory
Adrian M. Stütz, European Molecular Biology Laboratory Heidelberg
Xinghua Shi, The University of North Carolina at Charlotte
Francesco Paolo Casale, Wellcome Trust
Jieming Chen, Yale University
Fereydoun Hormozdiari, University of Washington, Seattle
Gargi Dayama, University of Michigan, Ann Arbor
Ken Chen, University of Texas MD Anderson Cancer Center
Maika Malig, University of Washington, Seattle
Mark J.P. Chaisson, University of Washington, Seattle
Klaudia Walter, Wellcome Trust
Sascha Meiers, European Molecular Biology Laboratory Heidelberg
Seva Kashin, Harvard Medical School
Erik Garrison, Boston College
Adam Auton, Albert Einstein College of Medicine of Yeshiva University
Hugo Y.K. Lam, Bina Technologies
Xinmeng Jasmine Mu, Yale University
Can Alkan, Bilkent Üniversitesi
Danny Antaki, University of California, San Diego
Taejeong Bae, Mayo Clinic
Eliza Cerveira, Jackson Laboratory
Peter Chines, National Human Genome Research Institute (NHGRI)
Zechen Chong, University of Texas MD Anderson Cancer Center

Document Type

Article

Publication Date

9-30-2015

Abstract

© 2015 Macmillan Publishers Limited. All rights reserved. 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.

Publication Source (Journal or Book title)

Nature

First Page

75

Last Page

81

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