Genetic analysis of von Willebrand's disease in two large pedigrees: a multivariate approach.

Clinical and laboratory data, including polymorphic marker traits for linkage analysis, were collected from two large multigenerational families segregating for von Willebrand disease. A new approach to the identification of gene carriers in these families, combining pedigree segregation analysis with multivariate discriminant analysis, is applied. Whereas individually the clinical symptoms and the factor VIII related activities could not distinguish between hypotheses, it was possible to find a discriminant function-showing consistency of the data with a dominant gene hypothesis, but not with a recessive gene or an environmental hypothesis. This function is estimated to lead to 3.2% and 5.5% minimum misclassification of the genotypes, respectively, in the two families. The discriminant function could be used for other families, but is should be calibrated for the specific population in which it is used. Among the markers investigated, GPT is the most likely to be linked to von Willbrand's disease, with a maximum lod score of about unity at 15% recombination.

从两个患有血管性血友病的大型多代家族中收集了临床和实验室数据，包括用于连锁分析的多态性标记特征。应用了一种新的方法来识别这些家族中的基因携带者，该方法将家系分离分析与多元判别分析相结合。虽然单独的临床症状和凝血因子VIII相关活性无法区分不同的假设，但有可能找到一个判别函数，该函数表明数据与显性基因假设一致，而与隐性基因或环境假设不一致。据估计，在这两个家族中，该函数分别导致基因型的最小错误分类率为3.2%和5.5%。判别函数可用于其他家族，但应针对其使用的特定人群进行校准。在所研究的标记中，谷丙转氨酶（GPT）最有可能与血管性血友病相关联，在15%重组率时最大优势对数计分约为1。