Jin L, Chakraborty R
Center for Demographic and Population Genetics, Graduate School of Biomedical Sciences, University of Texas, Houston 77225.
Heredity (Edinb). 1995 Mar;74 ( Pt 3):274-85. doi: 10.1038/hdy.1995.41.
In a substructured population the overall heterozygote deficiency can be predicted from the number of subpopulations (s), their time of divergence (t), and the nature of the mutations. At present the true mutational mechanisms at the hypervariable DNA loci are not known. However, the two existing mutation models (the infinite allele model (IAM) and the stepwise mutation model (SMM)) provide some guides to predictions from which the possible effect of population substructuring may be evaluated, assuming that the subpopulations do not exchange any genes among them during evolution. The theory predicts that the loci with larger mutation rate, and consequently showing greater heterozygosity within subpopulations, should exhibit a smaller proportional heterozygote deficiency (GST) and, hence, the effects of population substructuring should be minimal at the hypervariable DNA loci (an order of magnitude smaller than that at the blood group and protein loci). Applications of this theory to data on six Variable Number of Tandem Repeat (VNTR) loci and five short tandem repeat (STR) loci in the major cosmopolitan populations of the USA show that while the VNTR loci often exhibit a large significant heterozygote deficiency, the STR loci do not show a similar tendency. This discordant finding may be ascribed to the limitations, coalescence and nondetectability of alleles associated with the restriction fragment length polymorphism (RFLP) analysis through which the VNTR loci are scored. Such limitations do not apply to the polymerase chain reaction (PCR) method, through which the STR loci are scored. The implications of these results are discussed in the context of the forensic use of DNA typing data.
在一个亚结构化群体中，总体杂合子缺失情况可根据亚群体数量（s）、它们的分化时间（t）以及突变的性质来预测。目前，高变DNA位点的真正突变机制尚不清楚。然而，现有的两种突变模型（无限等位基因模型（IAM）和逐步突变模型（SMM））为预测提供了一些指导，据此可以评估群体亚结构化可能产生的影响，前提是亚群体在进化过程中不进行任何基因交换。该理论预测，突变率较高、因而在亚群体中表现出更大杂合性的位点，应表现出较小比例的杂合子缺失（GST），因此，群体亚结构化对高变DNA位点的影响应最小（比血型和蛋白质位点的影响小一个数量级）。将该理论应用于美国主要世界性群体中六个串联重复可变数（VNTR）位点和五个短串联重复（STR）位点的数据表明，虽然VNTR位点常常表现出显著的大杂合子缺失，但STR位点并未表现出类似趋势。这一不一致的发现可能归因于与通过限制性片段长度多态性（RFLP）分析对VNTR位点进行评分相关等位基因的局限性、合并及不可检测性。这些局限性不适用于对STR位点进行评分的聚合酶链反应（PCR）方法。本文在DNA分型数据的法医应用背景下讨论了这些结果的意义。
