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

Don Conrad, Dalila Pinto, Richard Redon, Lars Feuk, Omer Gokcumen, Yujun Zhang, Jan Aerts, T. Daniel Andrews, Chris Barnes, Peter Campbell, Tomas Fitzgerald, Min Hu, Chun Hwa Ihm, Kati Kristiansson, Daniel G. MacArthur, Jeffrey R. MacDonald, Ifejinelo Onyiah, Andy Wing Chun Pang, Sam Robson, Kathy Stirrups & 8 others Armand Valsesia, Klaudia Walter, John Wei, Chris Tyler-Smith, Nigel P. Carter, Charles Lee, Stephen W. Scherer, Matthew E. Hurles

Research output: Contribution to journalArticle

1179 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)704-712
Number of pages9
JournalNature
Volume464
Issue number7289
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

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Human Genome
Single Nucleotide Polymorphism
Genome-Wide Association Study
DNA
Disease Susceptibility
Linkage Disequilibrium
Oligonucleotide Array Sequence Analysis
Base Pairing
Genotype
Genome

ASJC Scopus subject areas

  • General

Cite this

Conrad, D., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., ... Hurles, M. E. (2010). Origins and functional impact of copy number variation in the human genome. Nature, 464(7289), 704-712. https://doi.org/10.1038/nature08516

Origins and functional impact of copy number variation in the human genome. / Conrad, Don; Pinto, Dalila; Redon, Richard; Feuk, Lars; Gokcumen, Omer; Zhang, Yujun; Aerts, Jan; Andrews, T. Daniel; Barnes, Chris; Campbell, Peter; Fitzgerald, Tomas; Hu, Min; Ihm, Chun Hwa; Kristiansson, Kati; MacArthur, Daniel G.; MacDonald, Jeffrey R.; Onyiah, Ifejinelo; Pang, Andy Wing Chun; Robson, Sam; Stirrups, Kathy; Valsesia, Armand; Walter, Klaudia; Wei, John; Tyler-Smith, Chris; Carter, Nigel P.; Lee, Charles; Scherer, Stephen W.; Hurles, Matthew E.

In: Nature, Vol. 464, No. 7289, 01.04.2010, p. 704-712.

Research output: Contribution to journalArticle

Conrad, D, Pinto, D, Redon, R, Feuk, L, Gokcumen, O, Zhang, Y, Aerts, J, Andrews, TD, Barnes, C, Campbell, P, Fitzgerald, T, Hu, M, Ihm, CH, Kristiansson, K, MacArthur, DG, MacDonald, JR, Onyiah, I, Pang, AWC, Robson, S, Stirrups, K, Valsesia, A, Walter, K, Wei, J, Tyler-Smith, C, Carter, NP, Lee, C, Scherer, SW & Hurles, ME 2010, 'Origins and functional impact of copy number variation in the human genome', Nature, vol. 464, no. 7289, pp. 704-712. https://doi.org/10.1038/nature08516
Conrad D, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y et al. Origins and functional impact of copy number variation in the human genome. Nature. 2010 Apr 1;464(7289):704-712. https://doi.org/10.1038/nature08516
Conrad, Don ; Pinto, Dalila ; Redon, Richard ; Feuk, Lars ; Gokcumen, Omer ; Zhang, Yujun ; Aerts, Jan ; Andrews, T. Daniel ; Barnes, Chris ; Campbell, Peter ; Fitzgerald, Tomas ; Hu, Min ; Ihm, Chun Hwa ; Kristiansson, Kati ; MacArthur, Daniel G. ; MacDonald, Jeffrey R. ; Onyiah, Ifejinelo ; Pang, Andy Wing Chun ; Robson, Sam ; Stirrups, Kathy ; Valsesia, Armand ; Walter, Klaudia ; Wei, John ; Tyler-Smith, Chris ; Carter, Nigel P. ; Lee, Charles ; Scherer, Stephen W. ; Hurles, Matthew E. / Origins and functional impact of copy number variation in the human genome. In: Nature. 2010 ; Vol. 464, No. 7289. pp. 704-712.
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