Haines J L, Amos J, Attwood J, Bech-Hansen N T, Burley M, Conneally P M, Connor J M, Fahsold R, Flodman P, Fryer A
Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Boston.
Ann N Y Acad Sci. 1991;615:256-64. doi: 10.1111/j.1749-6632.1991.tb37767.x.
Tuberous sclerosis (TSC) is a multisystem autosomal dominant hamartosis whose genetics is complicated by reduced penetrance and widely varying clinical expression. Results of linkage analyses have variously suggested two different locations for a TSC gene. A collaborative dataset has been assembled to clarify the issue of genetic heterogeneity. We have now analyzed the data from a combined sample of 111 families. Using Ott's HOMOG programs, we completed three tests of homogeneity: (1) for chromosome 9q, (2) for chromosome 11q, and (3) for the combined 9q and 11q data. For test 1 the chi-square (1 df) was 21.54 (p less than 0.001), for test 2 the chi-square (1 df) was 0.13 (p greater than 0.35), and for test 3 the chi-square (2 df) was 37.61 (p less than 0.0001). Additionally, we examined the combined data for evidence that a third, as yet unlinked locus exists. Results of this last test were suggestive but not significant. Clearly loci for TSC are present on both chromosomes 9q and 11q. The maximum likelihood estimate of the proportion of chromosome 9q-linked families is 0.38, for chromosome 11q-linked families is 0.47, and for the unlinked type 0.15. Alternative explanations for these latter families include chance sampling of recombinants, nongenetic phenocopies, or misclassification.
结节性硬化症（TSC）是一种多系统常染色体显性错构瘤病，其遗传学因外显率降低和临床表现差异很大而变得复杂。连锁分析结果曾不同程度地提示TSC基因存在两个不同的定位。已收集了一个协作数据集以阐明遗传异质性问题。我们现在分析了来自111个家庭的合并样本的数据。使用奥特的HOMOG程序，我们完成了三项同质性检验：（1）针对9号染色体长臂（9q），（2）针对11号染色体长臂（11q），以及（3）针对9q和11q的合并数据。对于检验1，卡方值（1自由度）为21.54（p小于0.001），对于检验2，卡方值（1自由度）为0.13（p大于0.35），对于检验3，卡方值（2自由度）为37.61（p小于0.0001）。此外，我们检查了合并数据，以寻找是否存在第三个尚未连锁的基因座的证据。最后这项检验的结果具有提示性但不显著。显然，TSC的基因座存在于9q和11q两条染色体上。与9q连锁的家庭比例的最大似然估计值为0.38，与11q连锁的家庭比例为0.47，未连锁类型的比例为0.15。对于后一类家庭的其他解释包括重组体的偶然抽样、非遗传表型模拟或错误分类。
