Simultaneous estimation of all the parameters of a stepwise mutation model.
Simultaneous estimation of all the parameters of a stepwise mutation model.
复制标题
同时估计逐步突变模型的所有参数。
DOI：
10.1093/genetics/150.1.487
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发表时间：
1998
期刊：
影响因子：
3.3
通讯作者：
Chakraborty,R
中科院分区：
文献类型：
--
作者：
Fu,YX;Chakraborty,R
小卫星和微卫星是分布于真核生物基因组中的短重复序列，由于重复序列拷贝数的变化，许多重复序列具有高度的多态。由于突变以一种广义的逐步方式改变重复序列的拷贝数，逐步突变模型被广泛用于研究这些基因座的动态。我们提出了一种最小卡方(MCS)方法，用于同时估计逐步突变模型中的所有参数和样本的祖先等位基因类型。MCS估计器需要知道样本中特定大小的等位基因的平均数量，这可以使用由合并算法生成的蒙特卡罗样本进行估计。该方法被应用于8个人类群体和1个黑猩猩群体的7个(CA)n重复基因座的样本。参数的估计值表明，微卫星等位基因总体上有扩大大小的趋势，因为(1)每个突变都有轻微的导致大小增加的趋势，(2)平均大小的增加大于突变的平均大小的减少。我们的估计还表明，这些CA-重复基因座中的大多数都是按照多步突变模型而不是单步突变模型进化的。我们还引入了衡量祖先等位基因类型估计质量的几个量，似乎大多数估计的祖先等位基因类型是相当准确的。讨论了我们的分析的含义和该方法的潜在扩展。
Minisatellite and microsatellite are short tandemly repetitive sequences dispersed in eukaryotic genomes, many of which are highly polymorphic due to copy number variation of the repeats. Because mutation changes copy numbers of the repeat sequences in a generalized stepwise fashion, stepwise mutation models are widely used for studying the dynamics of these loci. We propose a minimum chi-square (MCS) method for simultaneous estimation of all the parameters in a stepwise mutation model and the ancestral allelic type of a sample. The MCS estimator requires knowing the mean number of alleles of a certain size in a sample, which can be estimated using Monte Carlo samples generated by a coalescent algorithm. The method is applied to samples of seven (CA)nrepeat loci from eight human populations and one chimpanzee population. The estimated values of parameters suggest that there is a general tendency for microsatellite alleles to expand in size, because (1) each mutation has a slight tendency to cause size increase and (2) the mean size increase is larger than the mean size decrease for a mutation. Our estimates also suggest that most of these CA-repeat loci evolve according to multistep mutation models rather than single-step mutation models. We also introduced several quantities for measuring the quality of the estimation of ancestral allelic type, and it appears that the majority of the estimated ancestral allelic types are reasonably accurate. Implications of our analysis and potential extensions of the method are discussed.