Microsatellite markers for linkage and association studies

Abstract

During the 1990s and the first several years of this century, microsatellites or short tandem repeats were the workhorse genetic markers for hypothesis-independent studies in human genetics, facilitating genome-wide linkage studies and allelic imbalance studies. However, the rise of higher throughput and cost-effective single-nucleotide polymorphism (SNP) platforms led to the era of the SNP for genome scans. Nevertheless, it is important to note that microsatellites remain highly informative and useful measures of genomic variation for linkage and association studies. Their continued advantage in complementing SNPs lies in their greater allelic diversity than biallelic SNPs as well as in their population history, in which single-step expansion or contraction of the tandem repeat on the background of ancestral SNP haplotypes can break up common haplotypes, leading to greater haplotype diversity within the linkage disequilibrium block of interest. In fact, microsatellites have starred in association studies leading to widely replicated discoveries of type 2 diabetes (TCF7L2) and prostate cancer genes (the 8q21 region). At the end of the day, it will be important to catalog all variation, including SNPs, microsatellites, copy number variations, and polymorphic inversions in human genetic studies. This article describes the utilities of microsatellites and experimental approaches in their use.