Asmussen M A, Clegg M T
Am J Hum Genet. 1982 May;34(3):369-80.
Two-locus population genetic models are analyzed to evaluate the utility of restriction fragment length polymorphisms for purposes of genetic counseling. It is shown that the linkage disequilibrium between a neutral marker and a tightly linked overdominant mutant will increase rapidly as the mutant moves to its polymorphic equilibrium. The linkage disequilibrium decays for deleterious recessive mutants. Two measures involving the linkage disequilibrium are investigated to determine how much information the transmission of the neutral marker provides about the transmission of the selected gene. In certain kinds of matings, where the parental two-locus genotypes and linkage phases are known, it is possible to determine whether or not a progeny is homozygous for the selected gene on the basis of the fetal genotype at the marker locus. A quantity of primary interest is the fraction of matings between individuals heterozygous for the selected gene in which exact diagnosis can be made in this way. The expected proportion of such matings, taken over all two-locus matings involving heterozygotes at the selected locus, is calculated as a function of the gene frequencies at the two loci and the linkage disequilibrium between them. This expected value is maximized when the linkage disequilibrium is at its maximum in absolute value. Fewer than half of all matings are informative if the linkage disequilibrium is small in magnitude or if the gene frequencies at the two loci are quite different. Consideration is also given to various conditional measures of association that may be useful when the parental two-locus genotypes are unknown. The results suggest that the utility of tightly linked neutral marker genes in predicting the transmission of a selected gene is generally less when selection acts against a recessive gene than for overdominant selection.
分析双基因座群体遗传模型，以评估限制性片段长度多态性在遗传咨询中的效用。结果表明，随着突变体达到其多态平衡，中性标记与紧密连锁的超显性突变体之间的连锁不平衡将迅速增加。对于有害隐性突变体，连锁不平衡会衰减。研究了两种涉及连锁不平衡的指标，以确定中性标记的传递能为所选基因的传递提供多少信息。在某些交配类型中，已知亲本的双基因座基因型和连锁相，就有可能根据标记基因座上的胎儿基因型来确定后代是否为所选基因的纯合子。一个主要关注的量是所选基因杂合个体之间交配的比例，在这些交配中可以通过这种方式进行准确诊断。对于所有涉及所选基因座杂合子的双基因座交配，计算这种交配的预期比例，作为两个基因座上基因频率及其之间连锁不平衡的函数。当连锁不平衡的绝对值最大时，该预期值最大。如果连锁不平衡程度较小或两个基因座上的基因频率差异很大，那么所有交配中只有不到一半是有信息价值的。还考虑了各种条件关联度量，当亲本双基因座基因型未知时，这些度量可能有用。结果表明，当选择作用于隐性基因时，紧密连锁的中性标记基因在预测所选基因传递方面的效用通常比超显性选择时要小。
