Hill W G, Weir B S
Institute of Cell, Animal and Population Biology, University of Edinburgh.
Am J Hum Genet. 1994 Apr;54(4):705-14.
Linkage disequilibrium, D, between a polymorphic disease and mapped markers can, in principle, be used to help find the map position of the disease gene. Likelihoods are therefore derived for the value of D conditional on the observed number of haplotypes in the sample and on the population parameter Nc, where N is the effective population size and c the recombination fraction between the disease and marker loci. The likelihood is computed explicitly for the case of two loci with heterozygote superiority and, more generally, by computer simulations assuming a steady state of constant population size and selective pressures or neutrality. It is found that the likelihood is, in general, not very dependent on the degree of selection at the loci and is very flat. This suggests that precise information on map position will not be obtained from estimates of linkage disequilibrium.
原则上，多态性疾病与已定位标记之间的连锁不平衡D可用于帮助确定疾病基因的图谱位置。因此，根据样本中观察到的单倍型数量以及群体参数Nc（其中N是有效群体大小，c是疾病与标记位点之间的重组率），推导出D值的似然性。对于具有杂合子优势的两个位点的情况，明确计算了似然性，更一般地，通过计算机模拟，假设群体大小和选择压力恒定或处于中性的稳态。结果发现，似然性通常不太依赖于位点的选择程度，并且非常平缓。这表明从连锁不平衡估计中无法获得关于图谱位置的精确信息。
