Laboratory Methods for High-Throughput Genotyping

The genetics of complex diseases has been given a tremendous boost in recent years by the introduction of high-throughput laboratory methods that make it possible to approach larger questions in larger populations and to cover the genome more comprehensively. The ability to determine genotypes of many individuals accurately and efficiently has allowed genetic studies that cover more of the variation within individual genes, instead of focusing only on one or a few coding variants, and to do so in study samples of reasonable power. Chip-based genotyping assays, combined with knowledge of the patterns of coinheritance of markers (linkage disequilibrium [LD]), have stimulated genome-wide association studies (GWAS) of complex diseases. Recent successes of GWAS in identifying specific genes that affect risk for common diseases are dramatic illustrations of how improved technology can lead to scientific breakthroughs. A key issue in high-throughput genotyping is to choose the appropriate technology for your goals and for the stage of your experiment, being cognizant of your sample numbers and resources. This article introduces some of the commonly used methods of high-throughput single-nucleotide polymorphism (SNP) genotyping for different stages of genetic studies and briefly reviews some of the high-throughput sequencing methods just coming into use. It also mentions some recent developments in “next-generation” sequencing that will enable other kinds of studies. This article is not intended to be comprehensive, and because technology in this area is rapidly changing, our comments should be taken as a starting point for further investigation.