Scientific Publications

Integrated detection and population-genetic analysis of SNPs and copy number variation.

Publication TypeJournal Article
AuthorsMcCarroll, SA, Kuruvilla FG, Korn JM, Cawley S., Nemesh J., Wysoker A., Shapero MH, de Bakker PI, Maller JB, Kirby A., Elliott AL, Parkin M., Hubbell E., Webster T., Mei R., Veitch J., Collins PJ, Handsaker R., Lincoln S., Nizzari M., Blume J., Jones KW, Rava R., Daly M. J., Gabriel SB, and Altshuler D.
AbstractDissecting the genetic basis of disease risk requires measuring all forms of genetic variation, including SNPs and copy number variants (CNVs), and is enabled by accurate maps of their locations, frequencies and population-genetic properties. We designed a hybrid genotyping array (Affymetrix SNP 6.0) to simultaneously measure 906,600 SNPs and copy number at 1.8 million genomic locations. By characterizing 270 HapMap samples, we developed a map of human CNV (at 2-kb breakpoint resolution) informed by integer genotypes for 1,320 copy number polymorphisms (CNPs) that segregate at an allele frequency >1%. More than 80% of the sequence in previously reported CNV regions fell outside our estimated CNV boundaries, indicating that large (>100 kb) CNVs affect much less of the genome than initially reported. Approximately 80% of observed copy number differences between pairs of individuals were due to common CNPs with an allele frequency >5%, and more than 99% derived from inheritance rather than new mutation. Most common, diallelic CNPs were in strong linkage disequilibrium with SNPs, and most low-frequency CNVs segregated on specific SNP haplotypes.
Year of Publication2008
JournalNature genetics
Volume40
Issue10
Pages1166-74
Date Published (YYYY/MM/DD)2008/10/01
ISSN Number1061-4036
DOI10.1038/ng.238
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/18776908?dopt=Abstract