Kaplan N, Weir B S
Division of Biometry and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Am J Hum Genet. 1992 Aug;51(2):333-43.
The ubiquitousness of RFLPs in the human genome has greatly helped the mapping of human disease genes, and it has been suggested that population measures of association between disease and marker loci could help with this mapping. For rare diseases, random samples are taken from within disease genotypes in order to obtain reasonable sample sizes, but this sampling strategy requires a modification of the usual measures of association. We present theoretical predictions for the mean and variance of such a modified measure, under the assumption that the disease gene is maintained at a constant low frequency in the population. The coefficient of variation of this modified measure is large enough that caution is needed in using the measure to locate disease genes, and, furthermore, the coefficient of variation cannot be made arbitrarily small by increasing sample size. The modified association measure is calculated for recently published data on cystic fibrosis.
限制性片段长度多态性（RFLP）在人类基因组中的普遍性极大地推动了人类疾病基因的定位，并且有人提出，疾病与标记位点之间关联的群体测量方法有助于这种定位。对于罕见疾病，为了获得合理的样本量，会从疾病基因型中随机抽样，但这种抽样策略需要对通常的关联测量方法进行修改。我们在疾病基因在群体中以恒定低频率维持的假设下，给出了这种修改后测量方法的均值和方差的理论预测。这种修改后测量方法的变异系数足够大，以至于在使用该方法定位疾病基因时需要谨慎，此外，变异系数不能通过增加样本量而任意减小。针对最近发表的囊性纤维化数据计算了修改后的关联测量值。
