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Origins and functional impact of copy number variation in the human genome

Conrad, Donald; Pinto, Dalila; Redon, Richard; Feuk, Lars; Gokcumen, Omer; Zhang, Yujun; Aerts, Jan; Andrews, Thomas Daniel; Barnes, Chris; Campbell, Peter; Fitzgerald, Tomas

Description

Structural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or...[Show more]

dc.contributor.authorConrad, Donald
dc.contributor.authorPinto, Dalila
dc.contributor.authorRedon, Richard
dc.contributor.authorFeuk, Lars
dc.contributor.authorGokcumen, Omer
dc.contributor.authorZhang, Yujun
dc.contributor.authorAerts, Jan
dc.contributor.authorAndrews, Thomas Daniel
dc.contributor.authorBarnes, Chris
dc.contributor.authorCampbell, Peter
dc.contributor.authorFitzgerald, Tomas
dc.date.accessioned2015-12-08T22:45:22Z
dc.identifier.issn0028-0836
dc.identifier.urihttp://hdl.handle.net/1885/37802
dc.description.abstractStructural variations of DNA greater than 1 kilobase in size account for most bases that vary among human genomes, but are still relatively under-ascertained. Here we use tiling oligonucleotide microarrays, comprising 42 million probes, to generate a comprehensive map of 11,700 copy number variations (CNVs) greater than 443 base pairs, of which most (8,599) have been validated independently. For 4,978 of these CNVs, we generated reference genotypes from 450 individuals of European, African or East Asian ancestry. The predominant mutational mechanisms differ among CNV size classes. Retrotransposition has duplicated and inserted some coding and non-coding DNA segments randomly around the genome. Furthermore, by correlation with known trait-associated single nucleotide polymorphisms (SNPs), we identified 30 loci with CNVs that are candidates for influencing disease susceptibility. Despite this, having assessed the completeness of our map and the patterns of linkage disequilibrium between CNVs and SNPs, we conclude that, for complex traits, the heritability void left by genome-wide association studies will not be accounted for by common CNVs.
dc.publisherMacmillan Publishers Ltd
dc.sourceNature
dc.subjectKeywords: DNA; genome; genotype; hominid; article; disease predisposition; DNA microarray; gene linkage disequilibrium; gene locus; gene mutation; genetic variability; genotype; heritability; human genome; priority journal; single nucleotide polymorphism; Continent
dc.titleOrigins and functional impact of copy number variation in the human genome
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume464
dc.date.issued2010
local.identifier.absfor060408 - Genomics
local.identifier.ariespublicationu6800332xPUB153
local.type.statusPublished Version
local.contributor.affiliationConrad, Donald, Wellcome Trust Genome Campus
local.contributor.affiliationPinto, Dalila, The Hospital for Sick Children
local.contributor.affiliationRedon, Richard, Wellcome Trust Genome Campus
local.contributor.affiliationFeuk, Lars, The Hospital for Sick Children
local.contributor.affiliationGokcumen, Omer, Harvard Medical School
local.contributor.affiliationZhang, Yujun, Wellcome Trust Genome Campus
local.contributor.affiliationAerts, Jan, Wellcome Trust Genome Campus
local.contributor.affiliationAndrews, Thomas Daniel, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBarnes, Chris, Wellcome Trust Genome Campus
local.contributor.affiliationCampbell, Peter, Wellcome Trust Genome Campus
local.contributor.affiliationFitzgerald, Tomas, The Wellcome Trust Genome Campus
local.description.embargo2037-12-31
local.bibliographicCitation.startpage704
local.bibliographicCitation.lastpage712
local.identifier.doi10.1038/nature08516
dc.date.updated2016-02-24T11:37:59Z
local.identifier.scopusID2-s2.0-77950461601
CollectionsANU Research Publications

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