title: Integrated detection and population-genetic analysis of SNPs and copy number variation.
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.
authors.affiliation: Program in Medical and Population Genetics and Genetic Analysis Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
authors.forename: Finny G
authors.initials: FG
authors.lastname: Kuruvilla
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Korn
authors.forename: Simon
authors.initials: S
authors.lastname: Cawley
authors.forename: James
authors.initials: J
authors.lastname: Nemesh
authors.forename: Alec
authors.initials: A
authors.lastname: Wysoker
authors.forename: Michael H
authors.initials: MH
authors.lastname: Shapero
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Julian B
authors.initials: JB
authors.lastname: Maller
authors.forename: Andrew
authors.initials: A
authors.lastname: Kirby
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Elliott
authors.forename: Melissa
authors.initials: M
authors.lastname: Parkin
authors.forename: Earl
authors.initials: E
authors.lastname: Hubbell
authors.forename: Teresa
authors.initials: T
authors.lastname: Webster
authors.forename: Rui
authors.initials: R
authors.lastname: Mei
authors.forename: James
authors.initials: J
authors.lastname: Veitch
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Collins
authors.forename: Robert
authors.initials: R
authors.lastname: Handsaker
authors.forename: Steve
authors.initials: S
authors.lastname: Lincoln
authors.forename: Marcia
authors.initials: M
authors.lastname: Nizzari
authors.forename: John
authors.initials: J
authors.lastname: Blume
authors.forename: Keith W
authors.initials: KW
authors.lastname: Jones
authors.forename: Rich
authors.initials: R
authors.lastname: Rava
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Stacey B
authors.initials: SB
authors.lastname: Gabriel
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics*
chemical_list: D004247:DNA