TY - JOUR
T1 - Origins and functional impact of copy number variation in the human genome
AU - Conrad, Donald F.
AU - Pinto, Dalila
AU - Redon, Richard
AU - Feuk, Lars
AU - Gokcumen, Omer
AU - Zhang, Yujun
AU - Aerts, Jan
AU - Andrews, T. Daniel
AU - Barnes, Chris
AU - Campbell, Peter
AU - Fitzgerald, Tomas
AU - Hu, Min
AU - Ihm, Chun Hwa
AU - Kristiansson, Kati
AU - MacArthur, Daniel G.
AU - MacDonald, Jeffrey R.
AU - Onyiah, Ifejinelo
AU - Pang, Andy Wing Chun
AU - Robson, Sam
AU - Stirrups, Kathy
AU - Valsesia, Armand
AU - Walter, Klaudia
AU - Wei, John
AU - Tyler-Smith, Chris
AU - Carter, Nigel P.
AU - Lee, Charles
AU - Scherer, Stephen W.
AU - Hurles, Matthew E.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/77950461601
U2 - 10.1038/nature08516
DO - 10.1038/nature08516
M3 - Article
C2 - 19812545
AN - SCOPUS:77950461601
SN - 0028-0836
VL - 464
SP - 704
EP - 712
JO - Nature
JF - Nature
IS - 7289
ER -