title: Large-scale genotyping of complex DNA.
abstract: Genetic studies aimed at understanding the molecular basis of complex human phenotypes require the genotyping of many thousands of single-nucleotide polymorphisms (SNPs) across large numbers of individuals. Public efforts have so far identified over two million common human SNPs; however, the scoring of these SNPs is labor-intensive and requires a substantial amount of automation. Here we describe a simple but effective approach, termed whole-genome sampling analysis (WGSA), for genotyping thousands of SNPs simultaneously in a complex DNA sample without locus-specific primers or automation. Our method amplifies highly reproducible fractions of the genome across multiple DNA samples and calls genotypes at >99% accuracy. We rapidly genotyped 14,548 SNPs in three different human populations and identified a subset of them with significant allele frequency differences between groups. We also determined the ancestral allele for 8,386 SNPs by genotyping chimpanzee and gorilla DNA. WGSA is highly scaleable and enables the creation of ultrahigh density SNP maps for use in genetic studies.
authors.affiliation: Affymetrix, 3380 Central Expressway, Santa Clara, California 95051, USA. giulia_kennedy@affymetrix.com
authors.forename: Giulia C
authors.initials: GC
authors.lastname: Kennedy
authors.forename: Hajime
authors.initials: H
authors.lastname: Matsuzaki
authors.forename: Shoulian
authors.initials: S
authors.lastname: Dong
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Guoying
authors.initials: G
authors.lastname: Liu
authors.forename: Xing
authors.initials: X
authors.lastname: Su
authors.forename: Manqiu
authors.initials: M
authors.lastname: Cao
authors.forename: Wenwei
authors.initials: W
authors.lastname: Chen
authors.forename: Jane
authors.initials: J
authors.lastname: Zhang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Yang
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Di
authors.forename: Thomas
authors.initials: T
authors.lastname: Ryder
authors.forename: Zhijun
authors.initials: Z
authors.lastname: He
authors.forename: Urvashi
authors.initials: U
authors.lastname: Surti
authors.forename: Michael S
authors.initials: MS
authors.lastname: Phillips
authors.forename: Michael T
authors.initials: MT
authors.lastname: Boyce-Jacino
authors.forename: Stephen P A
authors.initials: SP
authors.lastname: Fodor
authors.forename: Keith W
authors.initials: KW
authors.lastname: Jones
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D005787:Gene Frequency / Q000235:genetics; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*; D012689:Sequence Homology, Nucleic Acid
chemical_list: D004247:DNA