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

Autor: Oliver Stegle, Ken Chen, Scott E. Devine, Mark Gerstein, Charles Lee, Eliza Cerveira, Klaudia Walter, Mallory Romanovitch, Evan E. Eichler, Nicholas F. Parrish, Shane A. McCarthy, Miriam K. Konkel, Steven A. McCarroll, Jing Zhang, Robert Sebra, Min Wang, Eric-Wubbo Lameijer, Gabor T. Marth, Seva Kashin, Xiangqun Zheng-Bradley, Tobias Rausch, Kai Ye, Chengsheng Zhang, Andrey A. Shabalin, Francesco Paolo Casale, Andreas Schlattl, Mark Chaisson, Jerilyn A. Walker, Jieming Chen, Fuli Yu, Christopher E. Mason, Richard A. Gibbs, Li Ding, Bradley J. Nelson, Paul Flicek, Adam Auton, Matthew Pendleton, Eugene J. Gardner, Andrew Quitadamo, Zechen Chong, John Huddleston, Markus His Yang Fritz, Ankit Malhotra, Taejeong Bae, Laura Clarke, Yan Zhang, Fereydoun Hormozdiari, Danny Antaki, Goo Jun, Amina Noor, Gargi Dayama, Sascha Meiers, Elif Dal, Adrian M. Stütz, Peter S. Chines, Eric E. Schadt, Yu Kong, Thomas Zichner, Benjamin Raeder, Andreas Untergasser, Jan O. Korbel, Donna M. Muzny, Xinghua Shi, Peter H. Sudmant, Madhusudan Gujral, Alexej Abyzov, Hugo Y. K. Lam, Maika Malig, Mark A. Batzer, Robert E. Handsaker, Ryan E. Mills, Xian Fan, Xinmeng Jasmine Mu, Ali Bashir, Jeffrey M. Kidd, S. Emery, Can Alkan, Fatma Kahveci, Wanding Zhou, Androniki Menelaou, Erik Garrison, Jonathan Sebat
Rok vydání: 2015
Předmět:
Unclassified drug
Gene loss
Intron
Genome-wide association study
Homozygosity
Gene inactivation
0302 clinical medicine
Human genetics
Mutation Rate
Haplotype
Priority journal
Sequence Deletion
Genetics
0303 health sciences
education.field_of_study
Multidisciplinary
Homozygote
Gene linkage disequilibrium
Genomics
Physical Chromosome Mapping
Polymerase chain reaction
Untranslated region
Human
Quantitative trait locus
Genotype
Clinical article
Genetics
Medical
Population
Genomic Structural Variation
Molecular Sequence Data
Quantitative Trait Loci
DNA sequence
Computational biology
Biology
Polymorphism
Single Nucleotide
Structural variation
03 medical and health sciences
Disease association
Humans
Genetic Predisposition to Disease
Amino Acid Sequence
education
Gene mapping
030304 developmental biology
Demography
Human genome
Genome
Human
Serine proteinase inhibitor
Genetic Variation
SPINK14 protein
Sequence Analysis
DNA
Single nucleotide polymorphism
Gene structure
Genetics
Population
Haplotypes
Expression quantitative trait loci
Genetic association
Genetic variability
Glycoprotein
030217 neurology & neurosurgery
Dual specificity phosphatase
Genome-Wide Association Study
Zdroj: Nature : international weekly journal of science
Nature
ISSN: 1476-4687
Popis: 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.
Databáze: OpenAIRE
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