Gulcher Jeffrey
Cold Spring Harb Protoc. 2012 Apr 1;2012(4):425-32. doi: 10.1101/pdb.top068510.
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.
在20世纪90年代和本世纪的头几年，微卫星或短串联重复序列是人类遗传学中用于非假设性研究的主要遗传标记，推动了全基因组连锁研究和等位基因不平衡研究。然而，更高通量且更具成本效益的单核苷酸多态性（SNP）平台的兴起开启了用于基因组扫描的SNP时代。尽管如此，需要注意的是，微卫星对于连锁和关联研究而言，仍然是极具信息价值且有用的基因组变异衡量指标。它们在补充SNP方面的持续优势在于，相较于双等位基因SNP，其具有更高的等位基因多样性，以及在其群体历史方面，即在祖先SNP单倍型背景下串联重复序列的单步扩增或收缩能够打破常见单倍型，从而在感兴趣的连锁不平衡区域内产生更高的单倍型多样性。事实上，微卫星在关联研究中发挥了重要作用，促成了2型糖尿病（TCF7L2）和前列腺癌基因（8q21区域）等诸多广泛重复验证的发现。归根结底，在人类遗传学研究中对所有变异进行编目，包括SNP、微卫星、拷贝数变异和多态性倒位，将具有重要意义。本文介绍了微卫星的用途及其使用中的实验方法。
