VNTR allele frequency distributions under the stepwise mutation model: a computer simulation approach.
VNTR allele frequency distributions under the stepwise mutation model: a computer simulation approach.
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DOI：
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发表时间：
1993-07
期刊：
影响因子：
3.3
通讯作者：
M. Shriver;L. Jin;Ranajit Chakraborty;E. Boerwinkle
中科院分区：
文献类型：
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作者：
M. Shriver;L. Jin;Ranajit Chakraborty;E. Boerwinkle
可变数串联重复序列（VNTRs）是一类信息丰富、分布广泛的遗传标记。尽管它们在生物科学中得到了广泛的应用，但人们对它们的突变机制和种群动态知之甚少。利用计算机模拟一步逐步突变模型（one-step step mutation model， SMM），研究了VNTR等位基因频率分布的四项综合指标：等位基因数量、模式数量、等位基因大小范围和杂合度。我们估计了这些测量值及其在大范围突变率下的概率分布，并将模拟结果与一步SMM分析公式的预测结果进行了比较。模拟得到的平均杂合度与SMM下的分析期望相符。然而，在模拟中，等位基因的平均数量比SMM的分析预期要大。然后，我们将模拟期望与文献中报道的实际数据进行了比较。我们使用样本量和观察到的杂合度来确定期望值，其他三个汇总测量的第5和第95百分位，等位基因大小范围，模式数和等位基因数。根据重复单位的大小，将分析的基因座分为微卫星（1-2个碱基对（bp）重复单位）、短串联重复[(STR) 3-5个bp重复单位]和小卫星（15-70个bp重复单位）3类。总体而言，STR位点在等位基因数量、模式数量和等位基因大小范围三个综合指标上与SMM下的模拟结果最相似，其次是微卫星位点，其次是小卫星位点，在无限等位基因模型（IAM）方向上存在偏差。基于这些差异，我们假设这三类基因座受到不同的突变力的影响。
Variable numbers of tandem repeats (VNTRs) are a class of highly informative and widely dispersed genetic markers. Despite their wide application in biological science, little is known about their mutational mechanisms or population dynamics. The objective of this work was to investigate four summary measures of VNTR allele frequency distributions: number of alleles, number of modes, range in allele size and heterozygosity, using computer simulations of the one-step stepwise mutation model (SMM). We estimated these measures and their probability distributions for a wide range of mutation rates and compared the simulation results with predictions from analytical formulations of the one-step SMM. The average heterozygosity from the simulations agreed with the analytical expectation under the SMM. The average number of alleles, however, was larger in the simulations than the analytical expectation of the SMM. We then compared our simulation expectations with actual data reported in the literature. We used the sample size and observed heterozygosity to determine the expected value, 5th and 95th percentiles for the other three summary measures, allelic size range, number of modes and number of alleles. The loci analyzed were classified into three groups based on the size of the repeat unit: microsatellites (1-2 base pair (bp) repeat unit), short tandem repeats [(STR) 3-5 bp repeat unit], and minisatellites (15-70 bp repeat unit). In general, STR loci were most similar to the simulation results under the SMM for the three summary measures (number of alleles, number of modes and range in allele size), followed by the microsatellite loci and then by the minisatellite loci, which showed deviations in the direction of the infinite allele model (IAM). Based on these differences, we hypothesize that these three classes of loci are subject to different mutational forces.