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

@article{citeulike:3225802, abstract = {Dissecting 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.}, address = {[1] Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. [2] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [4] Harvard Medical School, Boston, Massachusetts 02115, USA. [5] These authors contributed equally to this work.}, author = {McCarroll, Steven A. and Kuruvilla, Finny G. and Korn, Joshua M. and Cawley, Simon and Nemesh, James and Wysoker, Alec and Shapero, Michael H. and de Bakker, Paul I. and Maller, Julian B. and Kirby, Andrew and Elliott, Amanda L. and Parkin, Melissa and Hubbell, Earl and Webster, Teresa and Mei, Rui and Veitch, James and Collins, Patrick J. and Handsaker, Robert and Lincoln, Steve and Nizzari, Marcia and Blume, John and Jones, Keith W. and Rava, Rich and Daly, Mark J. and Gabriel, Stacey B. and Altshuler, David}, citeulike-article-id = {3225802}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ng.238}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/ng.238}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18776908}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18776908}, day = {7}, doi = {10.1038/ng.238}, issn = {1546-1718}, journal = {Nature genetics}, keywords = {bioinformatics, genetics, snps}, month = {October}, number = {10}, pages = {1166--1174}, posted-at = {2008-10-07 16:13:01}, priority = {2}, publisher = {Nature Publishing Group}, title = {Integrated detection and population-genetic analysis of SNPs and copy number variation.}, url = {http://dx.doi.org/10.1038/ng.238}, volume = {40}, year = {2008} }

TY - JOUR ID - citeulike:3225802 L3 - citeulike-article-id:3225802 N2 - Dissecting 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. IS - 10 JF - Nature genetics SN - 1546-1718 AD - [1] Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. [2] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [4] Harvard Medical School, Boston, Massachusetts 02115, USA. [5] These authors contributed equally to this work. EP - 1174 TI - Integrated detection and population-genetic analysis of SNPs and copy number variation. PB - Nature Publishing Group VL - 40 SP - 1166 KW - bioinformatics KW - genetics KW - snps AU - McCarroll, Steven AU - Kuruvilla, Finny AU - Korn, Joshua AU - Cawley, Simon AU - Nemesh, James AU - Wysoker, Alec AU - Shapero, Michael AU - de Bakker, Paul AU - Maller, Julian AU - Kirby, Andrew AU - Elliott, Amanda AU - Parkin, Melissa AU - Hubbell, Earl AU - Webster, Teresa AU - Mei, Rui AU - Veitch, James AU - Collins, Patrick AU - Handsaker, Robert AU - Lincoln, Steve AU - Nizzari, Marcia AU - Blume, John AU - Jones, Keith AU - Rava, Rich AU - Daly, Mark AU - Gabriel, Stacey AU - Altshuler, David PY - 2008/10/07/ UR - http://dx.doi.org/10.1038/ng.238 ER -