Martinez M, Goldin L R
Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, MD 20892.
Genet Epidemiol. 1990;7(3):219-30. doi: 10.1002/gepi.1370070306.
We have conducted a simulation study in small pedigrees to investigate the power to detect linkage and heterogeneity for a disorder due to either one of two independent disease loci. We have considered a highly polymorphic marker locus (PIC = 70%) linked to one disease locus and unlinked to the second. The power to detect linkage has been examined by using the admixture test. We have varied the mode of transmission of each disease locus, the ascertainment of families and the proportion of cases in the population due to the linked disease locus. Generally, for the multiplex ascertainments we have considered, the power to detect linkage is greater when the linked disease locus has a high penetrance, when the unlinked disease locus has a low penetrance, and when pedigrees with multiple affected are selected. When selecting families with multiple affected, the rate of "mixed" families (i.e., those segregating for both disease loci) increases. However, for the pedigree structure we have considered, the power of the linkage test is more affected by a decrease in the rate of "linked" families than by an increase in the rate of "mixed" families. Finally, the present study shows that detection of linkage in presence of heterogeneity is feasible with a realistic sample size of small pedigrees as long as the linked disease locus accounts for more than 25% of the cases.
我们在小家系中进行了一项模拟研究，以探究检测由两个独立疾病位点之一导致的疾病的连锁和遗传异质性的效能。我们考虑了一个与一个疾病位点连锁且与另一个疾病位点不连锁的高度多态性标记位点（PIC = 70%）。通过使用混合检验来检测连锁的效能。我们改变了每个疾病位点的传递模式、家系的确定方式以及人群中由连锁疾病位点导致的病例比例。一般来说，对于我们所考虑的多重确定家系，当连锁疾病位点具有高外显率、非连锁疾病位点具有低外显率以及选择有多个受累者的家系时，检测连锁的效能更高。当选择有多个受累者的家系时，“混合”家系（即两个疾病位点都分离的家系）的比例会增加。然而，对于我们所考虑的家系结构，连锁检验的效能受“连锁”家系比例降低的影响比受“混合”家系比例增加的影响更大。最后，本研究表明，只要连锁疾病位点占病例的比例超过25%，在存在遗传异质性的情况下，使用现实样本量的小家系来检测连锁是可行的。
