title: Origins and functional impact of copy number variation in the human genome.
abstract: 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 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.
authors.affiliation: The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA UK.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Conrad
authors.forename: Dalila
authors.initials: D
authors.lastname: Pinto
authors.forename: Richard
authors.initials: R
authors.lastname: Redon
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.forename: Omer
authors.initials: O
authors.lastname: Gokcumen
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jan
authors.initials: J
authors.lastname: Aerts
authors.forename: T Daniel
authors.initials: TD
authors.lastname: Andrews
authors.forename: Chris
authors.initials: C
authors.lastname: Barnes
authors.forename: Peter
authors.initials: P
authors.lastname: Campbell
authors.forename: Tomas
authors.initials: T
authors.lastname: Fitzgerald
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Chun Hwa
authors.initials: CH
authors.lastname: Ihm
authors.forename: Kati
authors.initials: K
authors.lastname: Kristiansson
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Macarthur
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Macdonald
authors.forename: Ifejinelo
authors.initials: I
authors.lastname: Onyiah
authors.forename: Andy Wing Chun
authors.initials: AW
authors.lastname: Pang
authors.forename: Sam
authors.initials: S
authors.lastname: Robson
authors.forename: Kathy
authors.initials: K
authors.lastname: Stirrups
authors.forename: Armand
authors.initials: A
authors.lastname: Valsesia
authors.forename: Klaudia
authors.initials: K
authors.lastname: Walter
authors.forename: John
authors.initials: J
authors.lastname: Wei
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics*; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016296:Mutagenesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044469:Racial Groups / Q000235:genetics; D015203:Reproducibility of Results