New Generation Pharmacogenomic Tools: A SNP Linkage Disequilibrium Map, Validated SNP Assay Resource, and High-Throughput Instrumentation System for Large-Scale Genetic Studies

Abstract

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies—specifically for candidate-gene, candidate-region, and whole-genome association studies—will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics’ human genome assembly and enormous resource of physically mapped SNPs (approximately 4 000 000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency of the polymorphisms. We also discuss an advanced, high-performance SNP assay chemistry—a new generation of the TaqMan® probe-based, 5′ nuclease assay—and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.