Falk C T
Ann Hum Genet. 1984 Jan;48(1):87-95. doi: 10.1111/j.1469-1809.1984.tb00838.x.
A model for genetic diseases and associated markers is defined where two distinct susceptibility alleles are possible, each associated with a different marker allele. Marker genotype distributions in a disease population are then expressed in terms of haplotype frequencies and penetrance parameters. It is shown that, if the heterozygote with two different disease alleles has a higher penetrance than the two disease homogzygotes, the observed to 'Hardy-Weinberg-expected' ratio of associated marker genotypes (the alpha/beta ratio of Falk, Mendell & Rubinstein, 1983) will always be greater than or equal to one. When all disease penetrances are equal, the model becomes indistinguishable from a recessive one-s-allele model with alpha/beta = 1. Application of these observations to several data sets for insulin dependent diabetes mellitus suggests the possibility that different marker genotype distributions in different samples may be due to different penetrances of the disease genotypes in the samples. If a particular environment causes the heterozygote disease genotype (with two different disease alleles) to have the highest penetrance, the marker genotype distribution would be compatible with the 2-s-allele model. In other environments where the three disease genotypes have essentially equal penetrances, the marker distribution would be compatible with the 1-s-allele model.
定义了一种遗传疾病及相关标记的模型，其中可能存在两种不同的易感等位基因，每种等位基因与不同的标记等位基因相关联。然后，根据单倍型频率和外显率参数来表示疾病群体中的标记基因型分布。结果表明，如果具有两种不同疾病等位基因的杂合子比两种疾病纯合子具有更高的外显率，那么观察到的相关标记基因型与“哈迪-温伯格预期”的比率（Falk、Mendell和Rubinstein，1983年的α/β比率）将始终大于或等于1。当所有疾病外显率相等时，该模型与α/β = 1的隐性单等位基因模型无法区分。将这些观察结果应用于几个胰岛素依赖型糖尿病数据集表明，不同样本中不同的标记基因型分布可能是由于样本中疾病基因型的不同外显率所致。如果特定环境导致杂合子疾病基因型（具有两种不同疾病等位基因）具有最高外显率，那么标记基因型分布将与双等位基因模型兼容。在其他三种疾病基因型外显率基本相等的环境中，标记分布将与单等位基因模型兼容。
