Goldin L R, Cox N J, Pauls D L, Gershon E S, Kidd K K
Genet Epidemiol. 1984;1(3):285-96. doi: 10.1002/gepi.1370010307.
Simulated multigenerational pedigrees were analyzed using the program GENPED and POINTER to examine the 1) limits of segregation analysis for detecting single locus, two-allele transmission of a dichotomous trait and 2) accuracy of the parameter estimates. Ten data sets of 30 pedigrees each (approximately 25 persons per pedigree) were simulated. The genotypic penetrance values were varied but the population prevalence of the trait was kept constant at 2%. For some data sets a linked marker locus was also simulated. Previous results had shown that a single major locus could be easily detected when the heterozygote penetrance (f1) was high or midway between the two homozygote penetrances. In this study, we found a single major locus could not be consistently detected by either method of segregation analysis when f1 was "low" to "intermediate." Accuracy of the parameter estimates depended on assumptions about the population prevalence. In those cases where the major locus could not be detected by segregation analysis, linkage to a marker locus could be detected as long as the marker was closely linked and there were not phenocopies in the population. Owing to the limited number of simulations in this study, we cannot generalize these findings. However, they provide a basis for further testing of methods of segregation analysis when factors such as the parameter values, family structure, and ascertainment scheme are varied.
使用GENPED和POINTER程序对模拟的多代系谱进行分析，以检验：1）用于检测二分性状单基因座、双等位基因传递的分离分析的局限性；2）参数估计的准确性。模拟了10组数据集，每组30个系谱（每个系谱约25人）。基因型外显率值有所变化，但性状的人群患病率保持在2%不变。对于一些数据集，还模拟了一个连锁标记位点。先前的结果表明，当杂合子外显率（f1）较高或在两个纯合子外显率之间时，单个主要基因座很容易被检测到。在本研究中，我们发现当f1为“低”到“中等”时，两种分离分析方法均无法一致地检测到单个主要基因座。参数估计的准确性取决于对人群患病率的假设。在那些通过分离分析无法检测到主要基因座的情况下，只要标记紧密连锁且人群中不存在拟表型，就可以检测到与标记位点的连锁。由于本研究中的模拟数量有限，我们无法推广这些发现。然而，它们为在参数值、家族结构和确定方案等因素变化时进一步测试分离分析方法提供了基础。
