Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci
Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci
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DOI：
10.1073/pnas.94.3.1041
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发表时间：
1997-02-04
影响因子：
11.1
通讯作者：
Deka, R
中科院分区：
文献类型：
--
作者：
Chakraborty, R;Kimmel, M;Deka, R
利用广义逐步突变模型，我们提出了一种估算微卫星基因座相对突变率的方法，该方法以重复基序为分组，利用方差分析对一组微卫星基因座上等位基因大小的分布进行分析，以重复基序类型为分组，我们估计了群体大小差异和基因座之间突变率差异的影响，从而提供了一个基序类型特异性突变率的估计值。对四组不同的二核苷酸、三核苷酸和四核苷酸位点的应用表明，平均而言，非致病微卫星位点的突变率与其基序大小成反比，二核苷酸的突变率似乎比四核苷酸高1.5-2倍，而非致病三核苷酸的突变率介于二核苷酸和四核苷酸之间。相比之下，致病的三核苷酸的突变率是四核苷酸的3.9-6.9倍。将这些估计值与微卫星上直接观察到的突变率进行比较表明，早先关于四核苷酸比二核苷酸突变率更高的建议可能源于直接突变测定中对四核苷酸位点的非随机抽样。
Using the generalized stepwise mutation model, we propose a method of estimating the relative mutation rates of microsatellite loci, grouped by the repeat motif, Applying ANOVA to the distributions of the allele sizes at microsatellite loci from a set of populations, grouped by repeat motif types, we estimated the effect of population size differences and mutation rate differences among loci, This provides an estimate of motif-type-specific mutation rates up to a multiplicative constant, Applications to four different sets of di-, tri-, and tetranucleotide loci from a number of human populations reveal that, on average, the non-disease-causing microsatellite loci have mutation rates inversely related to their motif sizes, The dinucleotides appear to have mutation rates 1.5-2 times higher than the tetranucleotides, and the non-disease-causing trinucleotides have mutation rates intermediate between the di- and tetranucleotides. In contrast, the disease-causing trinucleotides have mutation rates 3.9-6.9 times larger than the tetranucleotides, Comparison of these estimates with the direct observations of mutation rates at microsatellites indicates that the earlier suggestion of higher mutation rates of tetranucleotides in comparison with the dinucleotides may stem from a nonrandom sampling of tetranucleotide loci in direct mutation assays.