Merry A, Roger J H, Curnow R N
Ann Hum Genet. 1979 Jul;43(1):71-80. doi: 10.1111/j.1469-1809.1979.tb01550.x.
A model for the inheritance of a disease involving genes at just two linked loci is presented and discussed. One of the two pairs of opposite double homozygotes is assumed to lead to the disease and death. The other genotypes are assumed to be less fit than the double heterozygote. The cause of this reduced fitness may or may not be due to the disease. Conditions for the existence of a stable equilibrium are presented. The model has a sound biological basis and could be used to explain a wide range of disease frequencies and patterns of inheritance. Mutation is not required to explain why the disease persists in the population. Recurrence risks for sibs and twin concordance rates are derived and the consequences of the relaxation of selection against those with the disease are predicted. The effects of a selection model of the kind described on the amount of linkage disequilibrium in the population and on the estimation of the frequency of recombination are discussed.
本文提出并讨论了一种仅涉及两个连锁基因座的疾病遗传模型。假定两对相对的双纯合子中的一对会导致疾病和死亡。假定其他基因型的适应性低于双杂合子。这种适应性降低的原因可能与疾病有关，也可能无关。给出了存在稳定平衡的条件。该模型具有坚实的生物学基础，可用于解释广泛的疾病频率和遗传模式。无需用突变来解释疾病在人群中持续存在的原因。推导了同胞的复发风险和双胞胎的一致率，并预测了对患病人群选择放松的后果。讨论了上述选择模型对群体中连锁不平衡量以及重组频率估计的影响。
