Kennedy Giulia C, Matsuzaki Hajime, Dong Shoulian, Liu Wei-min, Huang Jing, Liu Guoying, Su Xing, Cao Manqiu, Chen Wenwei, Zhang Jane, Liu Weiwei, Yang Geoffrey, Di Xiaojun, Ryder Thomas, He Zhijun, Surti Urvashi, Phillips Michael S, Boyce-Jacino Michael T, Fodor Stephen P A, Jones Keith W
Affymetrix, 3380 Central Expressway, Santa Clara, California 95051, USA.
Nat Biotechnol. 2003 Oct;21(10):1233-7. doi: 10.1038/nbt869. Epub 2003 Sep 7.
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.
旨在理解复杂人类表型分子基础的遗传学研究需要对大量个体的成千上万个单核苷酸多态性（SNP）进行基因分型。到目前为止，公共项目已经识别出超过两百万个常见人类SNP；然而，对这些SNP进行评分需要耗费大量人力，并且需要大量自动化操作。在此，我们描述了一种简单而有效的方法，称为全基因组抽样分析（WGSA），用于在无需位点特异性引物或自动化操作的情况下，对复杂DNA样本中的成千个SNP同时进行基因分型。我们的方法能在多个DNA样本中扩增出基因组中高度可重复的片段，并以大于99%的准确率进行基因型判定。我们在三个不同的人类群体中快速对14,548个SNP进行了基因分型，并识别出其中在群体间存在显著等位基因频率差异的一个子集。我们还通过对黑猩猩和大猩猩DNA进行基因分型，确定了8,386个SNP的祖先等位基因。WGSA具有高度可扩展性，能够创建用于遗传学研究的超高密度SNP图谱。
