Goldgar D E, Lewis C M, Gholami K
Genetic Epidemiology Group, University of Utah, Salt Lake City.
Genet Epidemiol. 1993;10(6):383-8. doi: 10.1002/gepi.1370100609.
The multipoint identity-by-descent method was developed to detect linkage to a specific chromosomal region through partitioning the genetic variance. This method has previously been applied to quantitative traits, and here is extended to a qualitative trait, where a dichotomous affected/unaffected status variable is transformed to a quantitative variable by incorporating covariates. This method is applied to the Alzheimer's disease data sets from Genetic Analysis Workshop 8, to investigate putative linkage to chromosomes 19 and 21. The multipoint identity-by-descent method is used to test for linkage through the qualitative trait, and for excess sharing of the chromosomal region among affected sibs. Results are compared to those of the affected-pedigree-member method and classical linkage analysis. None of these methods gave results showing clear linkage, with the only marginally significant results occurring for the Boston data set on chromosome 19 and the Duke data set for chromosome 21 using the multipoint identity-by-descent method.
通过划分遗传方差来检测与特定染色体区域连锁的多位点同源方法得以发展。该方法此前已应用于数量性状，在此扩展至质量性状，即将二分的患病/未患病状态变量通过纳入协变量转化为数量变量。此方法应用于遗传分析研讨会8的阿尔茨海默病数据集，以研究与19号和21号染色体的假定连锁关系。多位点同源方法用于通过质量性状检测连锁关系，以及检测患病同胞中染色体区域的过度共享情况。将结果与患病家系成员法和经典连锁分析的结果进行比较。这些方法均未得出显示明确连锁的结果，仅使用多位点同源方法时，19号染色体的波士顿数据集和21号染色体的杜克数据集出现了勉强显著的结果。
