Lin H J, Rotter J I, Conte W J
Clin Genet. 1985 Sep;28(3):185-98. doi: 10.1111/j.1399-0004.1985.tb00386.x.
Based on a two-locus, double recessive model, we derive formulas for the risks that relatives of individuals with gluten-sensitive enteropathy (GSE) will also develop the disease. The calculations take advantage of: the linkage between the HLA locus and one of the two proposed GSE loci, and the preferential association of the HLA-DR3 and DR7 alleles with the GSE disease allele that occupies the HLA-linked locus. We use Bayes' rule to quantitate the strength of the association between the GSE disease allele and the HLA marker allele. This method predicts that siblings of the proband have an overall 10% risk for GSE, which is consistent with observed family data. This predicted risk rises to 30% when siblings are HLA-identical to the proband (also consistent with observed data) or when the sibling has the DR3 allele in the HLA haplotypes not shared with the proband. In those populations where DR7 also is associated with GSE, siblings of probands have a 10% predicted risk for GSE when only one HLA haplotype is shared with the proband and DR7 is included in the unshared haplotype. Other DR alleles are associated with much lower disease risks. By separating individuals into high and low risk groups, HLA typing identifies those individuals who would benefit from further diagnostic procedures. This general strategy should be applicable to other multilocus, marker-associated diseases.
基于双位点双隐性模型，我们推导出了患有麸质敏感性肠病（GSE）的个体的亲属患该疾病风险的公式。这些计算利用了：HLA位点与两个假定的GSE位点之一之间的连锁关系，以及HLA - DR3和DR7等位基因与占据HLA连锁位点的GSE疾病等位基因的优先关联。我们使用贝叶斯法则来量化GSE疾病等位基因与HLA标记等位基因之间关联的强度。该方法预测先证者的兄弟姐妹患GSE的总体风险为10%，这与观察到的家族数据一致。当兄弟姐妹与先证者HLA相同时（也与观察到的数据一致），或者当兄弟姐妹在与先证者不共享的HLA单倍型中具有DR3等位基因时，预测风险会升至30%。在DR7也与GSE相关的人群中，当先证者的兄弟姐妹仅与先证者共享一个HLA单倍型且未共享的单倍型中包含DR7时，预测患GSE的风险为10%。其他DR等位基因与疾病风险的关联要低得多。通过将个体分为高风险和低风险组，HLA分型可识别出那些将从进一步诊断程序中受益的个体。这种总体策略应适用于其他多位点、标记相关疾病。
