Mérette C, Lehner T, Ott J
Department of Psychiatry, Columbia University, New York, NY 10032.
Genet Epidemiol. 1993;10(6):455-9. doi: 10.1002/gepi.1370100621.
We present two new approaches to the problem of genetic heterogeneity encountered in linkage analysis of familial Alzheimer's disease. We used two-locus models to represent the possible existence of two disease genes while allowing for intrafamilial heterogeneity, and modeled the occurrence of the early onset form of the disease with epistasis. We developed a mixture model of heterogeneity where the early and late onset family types can be either linked to chromosome 19, 21, or unlinked, and where it is not necessary to arbitrarily preclassify a family into an early or late onset family type.
我们提出了两种新方法，用于解决在家族性阿尔茨海默病连锁分析中遇到的遗传异质性问题。我们使用双基因座模型来表示两个疾病基因可能的存在情况，同时考虑家族内的异质性，并通过上位性对疾病早发型的发生进行建模。我们开发了一种异质性混合模型，其中早发型和晚发型家族类型既可以与19号、21号染色体连锁，也可以不连锁，而且无需将一个家族任意预先分类为早发型或晚发型家族类型。
