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

@article{citeulike:5908971, 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.}, author = {Conrad, Donald F. and Pinto, Dalila and Redon, Richard and Feuk, Lars and Gokcumen, Omer and Zhang, Yujun and Aerts, Jan and Andrews, T. Daniel and Barnes, Chris and Campbell, Peter and Fitzgerald, Tomas and Hu, Min and Ihm, Chun H. and Kristiansson, Kati and MacArthur, Daniel G. and MacDonald, Jeffrey R. and Onyiah, Ifejinelo and Pang, Andy W. and Robson, Sam and Stirrups, Kathy and Valsesia, Armand and Walter, Klaudia and Wei, John and Tyler-Smith, Chris and Carter, Nigel P. and Lee, Charles and Scherer, Stephen W. and Hurles, Matthew E.}, booktitle = {Nature}, citeulike-article-id = {5908971}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature08516}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature08516}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19812545}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19812545}, day = {07}, doi = {10.1038/nature08516}, issn = {0028-0836}, journal = {Nature}, keywords = {cnv, copy, number, sequencing, variation}, month = {October}, posted-at = {2009-11-02 06:57:51}, priority = {2}, publisher = {Nature Publishing Group}, title = {Origins and functional impact of copy number variation in the human genome}, url = {http://dx.doi.org/10.1038/nature08516}, volume = {advance online publication}, year = {2009} }

TY - JOUR ID - citeulike:5908971 L3 - citeulike-article-id:5908971 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. JF - Nature SN - 0028-0836 TI - Origins and functional impact of copy number variation in the human genome PB - Nature Publishing Group VL - advance online publication T2 - Nature KW - cnv KW - copy KW - number KW - sequencing KW - variation AU - Conrad, Donald AU - Pinto, Dalila AU - Redon, Richard AU - Feuk, Lars AU - Gokcumen, Omer AU - Zhang, Yujun AU - Aerts, Jan AU - Andrews, Daniel AU - Barnes, Chris AU - Campbell, Peter AU - Fitzgerald, Tomas AU - Hu, Min AU - Ihm, Chun AU - Kristiansson, Kati AU - MacArthur, Daniel AU - MacDonald, Jeffrey AU - Onyiah, Ifejinelo AU - Pang, Andy AU - Robson, Sam AU - Stirrups, Kathy AU - Valsesia, Armand AU - Walter, Klaudia AU - Wei, John AU - Tyler-Smith, Chris AU - Carter, Nigel AU - Lee, Charles AU - Scherer, Stephen AU - Hurles, Matthew PY - 2009/10/07/ UR - http://dx.doi.org/10.1038/nature08516 ER -