Lai Yinglei, Sun Fengzhu
Department of Mathematics, Department of Biological Sciences, University of Southern California, USA.
Mol Biol Evol. 2003 Dec;20(12):2123-31. doi: 10.1093/molbev/msg228. Epub 2003 Aug 29.
Microsatellite markers are widely used for genetic studies, but the relationship between microsatellite slippage mutation rate and the number of repeat units remains unclear. In this study, microsatellite distributions in the human genome are collected from public sequence databases. We observe that there is a threshold size for slippage mutations. We consider a model of microsatellite mutation consisting of point mutations and single stepwise slippage mutations. From two sets of equations based on two stochastic processes and equilibrium assumptions, we estimate microsatellite slippage mutation rates without assuming any relationship between microsatellite slippage mutation rate and the number of repeat units. We use the least squares method with constraints to estimate expansion and contraction mutation rates. The estimated slippage mutation rate increases exponentially as the number of repeat units increases. When slippage mutations happen, expansion occurs more frequently for short microsatellites and contraction occurs more frequently for long microsatellites. Our results agree with the length-dependent mutation pattern observed from experimental data, and they explain the scarcity of long microsatellites.
微卫星标记广泛应用于遗传学研究，但微卫星滑动突变率与重复单元数量之间的关系仍不清楚。在本研究中，从公共序列数据库收集了人类基因组中的微卫星分布。我们观察到滑动突变存在一个阈值大小。我们考虑了一个由点突变和单步滑动突变组成的微卫星突变模型。基于两个随机过程和平衡假设的两组方程，我们在不假设微卫星滑动突变率与重复单元数量之间存在任何关系的情况下估计微卫星滑动突变率。我们使用带约束的最小二乘法来估计扩增和收缩突变率。估计的滑动突变率随着重复单元数量的增加呈指数增长。当发生滑动突变时，短微卫星更频繁地发生扩增，长微卫星更频繁地发生收缩。我们的结果与从实验数据中观察到的长度依赖性突变模式一致，并且解释了长微卫星的稀缺性。
