Haile R W, Iselius L, Hodge S E, Morton N E, Detels R
Hum Hered. 1981;31(4):252-8. doi: 10.1159/000153218.
40 multiplex multiple sclerosis (MS) families were analyzed for evidence of an MS susceptibility gene linked to the HLA region of the sixth chromosome. We assumed that population associations between specific HLA alleles and MS are due to linkage disequilibrium, so preference was given to hypotheses compatible with tight linkage, and explanations were sought for conflicting evidence. The analyses proceeded in two steps: (1) segregation analysis using the computer program POINTER, and (2) linkage analysis using LINKAS, first assuming linkage equilibrium and then allowing for linkage disequilibrium and etiological heterogeneity. The results of the segregation analyses were indeterminate. The results of the linkage analyses suggest that analyses that do not allow for disequilibrium lose substantial evidence on linkage. Of the models that were investigated under linkage disequilibrium, the best fit is with a model of complete linkage (theta= 0.0) in 75% of the pedigrees and no linkage in the remaining pedigrees. We were unable, however, to statistically reject another model involving loose linkage and no heterogeneity.
对40个多发性硬化症（MS）家系进行了分析，以寻找与第六条染色体的HLA区域相关的MS易感基因的证据。我们假定特定HLA等位基因与MS之间的群体关联是由于连锁不平衡所致，因此优先考虑与紧密连锁相符的假设，并对相互矛盾的证据进行解释。分析分两步进行：（1）使用计算机程序POINTER进行分离分析，以及（2）使用LINKAS进行连锁分析，首先假定连锁平衡，然后考虑连锁不平衡和病因异质性。分离分析的结果不确定。连锁分析的结果表明，不考虑不平衡的分析会在连锁方面失去大量证据。在连锁不平衡条件下研究的模型中，75%的家系最适合完全连锁模型（θ=0.0），其余家系无连锁。然而，我们无法从统计学上拒绝另一个涉及松散连锁且无异质性的模型。
