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

TitleAn integrated map of structural variation in 2,504 human genomes.
Publication TypeJournal Article
Year of Publication2015
AuthorsSudmant PH, Rausch T, Gardner EJ, Handsaker RE, Abyzov A, Huddleston J, Zhang Y, Ye K, Jun G, Fritz MHsi-Yang, Konkel MK, Malhotra A, St├╝tz AM, Shi X, Casale FPaolo, Chen J, Hormozdiari F, Dayama G, Chen K, Malig M, Chaisson MJP, Walter K, Meiers S, Kashin S, Garrison E, Auton A, Lam HYK, Mu XJasmine, Alkan C, Antaki D, Bae T, Cerveira E, Chines P, Chong Z, Clarke L, Dal E, Ding L, Emery S, Fan X, Gujral M, Kahveci F, Kidd JM, Kong Y, Lameijer E-W, McCarthy S, Flicek P, Gibbs RA, Marth G, Mason CE, Menelaou A, Muzny DM, Nelson BJ, Noor A, Parrish NF, Pendleton M, Quitadamo A, Raeder B, Schadt EE, Romanovitch M, Schlattl A, Sebra R, Shabalin AA, Untergasser A, Walker JA, Wang M, Yu F, Zhang C, Zhang J, Zheng-Bradley X, Zhou W, Zichner T, Sebat J, Batzer MA, McCarroll SA, Mills RE, Gerstein MB, Bashir A, Stegle O, Devine SE, Lee C, Eichler EE, Korbel JO
Corporate Authors1000 Genomes Project Consortium
JournalNature
Volume526
Issue7571
Pagination75-81
Date Published2015 Oct 01
ISSN1476-4687
KeywordsAmino Acid Sequence, Genetic Predisposition to Disease, Genetic Variation, Genetics, Medical, Genetics, Population, Genome, Human, Genome-Wide Association Study, Genomics, Genotype, Haplotypes, Homozygote, Humans, Molecular Sequence Data, Mutation Rate, Physical Chromosome Mapping, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sequence Analysis, DNA, 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.

DOI10.1038/nature15394
Alternate JournalNature
PubMed ID26432246
PubMed Central IDPMC4617611
Grant ListR01 HG002898 / HG / NHGRI NIH HHS / United States
P01HG007497 / HG / NHGRI NIH HHS / United States
WT085532/Z/08/Z / / Wellcome Trust / United Kingdom
S10 RR029676 / RR / NCRR NIH HHS / United States
R01 HG007068 / HG / NHGRI NIH HHS / United States
WT104947/Z/14/Z / / Wellcome Trust / United Kingdom
R01HG002898 / HG / NHGRI NIH HHS / United States
U41 HG007497 / HG / NHGRI NIH HHS / United States
R01GM59290 / GM / NIGMS NIH HHS / United States
RR19895 / RR / NCRR NIH HHS / United States
S10 RR019895 / RR / NCRR NIH HHS / United States
U41HG007497 / HG / NHGRI NIH HHS / United States
R01 GM059290 / GM / NIGMS NIH HHS / United States
RR029676-01 / RR / NCRR NIH HHS / United States
R01 CA166661 / CA / NCI NIH HHS / United States
R01CA166661 / CA / NCI NIH HHS / United States
T32 GM008666 / GM / NIGMS NIH HHS / United States
R01 HG002385 / HG / NHGRI NIH HHS / United States
104947 / / Wellcome Trust / United Kingdom
085532 / / Wellcome Trust / United Kingdom
R01HG007068 / HG / NHGRI NIH HHS / United States