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

Date
2015
Authors
Sudmant, P. H.
Rausch, T.
Gardner, E. J.
Handsaker, R. E.
Abyzov, A.
Huddleston, J.
Zhang, Y.
Ye, K.
Jun, G.
Fritz, M. Hsi-Yang
Advisor
Instructor
Source Title
Nature : international weekly journal of science
Print ISSN
0028-0836
Electronic ISSN
Publisher
Nature Publishing Group
Volume
526
Issue
Pages
75 - 81
Language
English
Type
Article
Journal Title
Journal ISSN
Volume Title
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.

Course
Other identifiers
Book Title
Keywords
Dual specificity phosphatase, Glycoprotein, Serine proteinase inhibitor, SPINK14 protein, Unclassified drug, Clinical article, Demography, Disease association, DNA sequence, Gene inactivation, Gene linkage disequilibrium, Gene loss, Gene mapping, Gene structure, Genetic association, Genetic variability, Genotype, Haplotype, Homozygosity, Human, Human genetics, Human genome, Intron, Polymerase chain reaction, Priority journal, Quantitative trait locus, Single nucleotide polymorphism, Untranslated region
Citation
Published Version (Please cite this version)