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

Nature
Authors
Peter Sudmant
Tobias Rausch
Eugene Gardner
Robert Handsaker
Alexej Abyzov
John Huddleston
Yan Zhang
Kai Ye
Goo Jun
Markus Fritz
Miriam Konkel
Ankit Malhotra
Adrian Stütz
Xinghua Shi
Francesco Casale
Jieming Chen
Fereydoun Hormozdiari
Gargi Dayama
Ken Chen
Maika Malig
Mark Chaisson
Klaudia Walter
Sascha Meiers
Seva Kashin
Erik Garrison
Adam Auton
Hugo Lam
Xinmeng Mu
Can Alkan
Danny Antaki
Taejeong Bae
Eliza Cerveira
Peter Chines
Zechen Chong
Laura Clarke
Elif Dal
Li Ding
Sarah Emery
Xian Fan
Madhusudan Gujral
Fatma Kahveci
Jeffrey Kidd
Yu Kong
Eric-Wubbo Lameijer
Shane McCarthy
Paul Flicek
Richard Gibbs
Gabor Marth
Christopher Mason
Androniki Menelaou
Donna Muzny
Bradley Nelson
Amina Noor
Nicholas Parrish
Matthew Pendleton
Andrew Quitadamo
Benjamin Raeder
Eric Schadt
Mallory Romanovitch
Andreas Schlattl
Robert Sebra
Andrey Shabalin
Andreas Untergasser
Jerilyn Walker
Min Wang
Fuli Yu
Chengsheng Zhang
Jing Zhang
Xiangqun Zheng-Bradley
Wanding Zhou
Thomas Zichner
Jonathan Sebat
Mark Batzer
Steven McCarroll
1000 Genomes Project Consortium
Ryan Mills
Mark Gerstein
Ali Bashir
Oliver Stegle
Scott Devine
Charles Lee
Evan Eichler
Jan Korbel
Keywords
Humans
Genetic Predisposition to Disease
Genomics
Genotype
Haplotypes
Molecular Sequence Data
Homozygote
Amino Acid Sequence
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Genetic Variation
Quantitative Trait Loci
Sequence Analysis, DNA
Genome, Human
Genetics, Medical
Genetics, Population
Mutation Rate
Physical Chromosome Mapping
Sequence Deletion
Abstract

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.
Year of Publication
2015
Journal
Nature
Volume
526
Issue
7571
Pages
75-81
Date Published
2015 Oct 1
ISSN
1476-4687
DOI
10.1038/nature15394
PubMed ID
26432246
PubMed Central ID
PMC4617611
Links
Grant list
085532 / Wellcome Trust / United Kingdom
104947 / Wellcome Trust / United Kingdom
P01HG007497 / HG / NHGRI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
R01 CA166661 / CA / NCI NIH HHS / United States
R01 HG002385 / HG / NHGRI NIH HHS / United States
R01 HG002898 / HG / NHGRI NIH HHS / United States
R01 HG007068 / HG / NHGRI NIH HHS / United States
R01CA166661 / CA / NCI NIH HHS / United States
R01GM59290 / GM / NIGMS NIH HHS / United States
R01HG002898 / HG / NHGRI NIH HHS / United States
R01HG007068 / HG / NHGRI NIH HHS / United States
RR029676-01 / RR / NCRR NIH HHS / United States
RR19895 / RR / NCRR NIH HHS / United States
T32 GM008666 / GM / NIGMS NIH HHS / United States
U41 HG007497 / HG / NHGRI NIH HHS / United States
U41HG007497 / HG / NHGRI NIH HHS / United States
WT085532/Z/08/Z / Wellcome Trust / United Kingdom
WT104947/Z/14/Z / Wellcome Trust / United Kingdom

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