Gunderson Kevin L, Kuhn Kenneth M, Steemers Frank J, Ng Pauline, Murray Sarah S, Shen Richard
Illumina, Inc., 9885 Towne Centre Dr., San Diego, CA 92121, USA.
Pharmacogenomics. 2006 Jun;7(4):641-8. doi: 10.2217/14622416.7.4.641.
The International HapMap Consortium recently completed genotyping over 3.8 million single nucleotide polymorphisms (SNPs) in three major populations, and the results of studying patterns of linkage disequilibrium indicate that characterization of 300,000-500,000 tag SNPs is sufficient to provide good genomic coverage for linkage-disequilibrium-based association studies in many populations. These whole-genome association studies will be used to dissect the genetics of complex diseases and pharmacogenomic drug responses. As such, the development of a cost-effective genotyping platform that can assay hundred of thousands of SNPs across thousands of samples is essential. In this review, we describe the development of a whole-genome genotyping (WGG) assay that enables unconstrained SNP selection and effectively unlimited multiplexing from a single sample preparation. The development of WGG in concert with high-density BeadChips has enabled the creation of three different high-density SNP genotyping BeadChips: the Sentrix Human-1 Genotyping BeadChip containing over 109,000 exon-centric SNPs; the HumanHap300 BeadChip containing over 317,000 tag SNPs, and the HumanHap550 Beadchip containing over 550,000 tag SNPs.
国际人类基因组单体型图协会最近完成了对三个主要人群中超过380万个单核苷酸多态性（SNP）的基因分型，对连锁不平衡模式的研究结果表明，鉴定30万至50万个标签SNP足以在许多人群中为基于连锁不平衡的关联研究提供良好的基因组覆盖。这些全基因组关联研究将用于剖析复杂疾病的遗传学和药物基因组学药物反应。因此，开发一种具有成本效益的基因分型平台至关重要，该平台能够对数千个样本中的数十万个SNP进行检测。在这篇综述中，我们描述了一种全基因组基因分型（WGG）检测方法的开发，该方法能够无限制地选择SNP，并能从单个样本制备中实现有效的无限多重分析。WGG与高密度微珠芯片协同开发，已能够创建三种不同的高密度SNP基因分型微珠芯片：包含超过109,000个以外显子为中心的SNP的Sentrix Human-1基因分型微珠芯片；包含超过317,000个标签SNP的HumanHap300微珠芯片，以及包含超过550,000个标签SNP的HumanHap550微珠芯片。
