Lin H J, Conte W J, Rotter J I
Clin Genet. 1985 Feb;27(2):127-33. doi: 10.1111/j.1399-0004.1985.tb00199.x.
The recessive hemochromatosis gene is both linked to the HLA region on chromosome 6 and nonrandomly associated with certain HLA alleles. The use of linked HLA markers to trace known hemochromatosis genes within a family is well known, but using the population associations to detect unsuspected disease genes has not been fully appreciated. Thus, while HLA typing has been utilized to detect asymptomatic affected siblings, it has not been applied to other relatives. We propose a method in which Bayes' rule is used to calculate the probability that designated HLA marker haplotypes, brought into the family by spouses, have attendant hemochromatosis genes. The A3, B14 and A3, B7 haplotypes are such high risk markers. When these haplotypes are inherited from the unaffected parent, the offspring of an individual with hemochromatosis is at marked increased risk for the disease. When A3 and B14 are absent from the HLA marker haplotype, however, the risk of having a hemochromatosis gene is less than that for the general population. This approach should be helpful in identifying family members at a higher risk for developing the disease and who may then undergo appropriate periodic screening.
隐性血色素沉着症基因既与6号染色体上的HLA区域连锁，又与某些HLA等位基因非随机关联。利用连锁的HLA标记来追踪家族中已知的血色素沉着症基因是众所周知的，但利用群体关联性来检测未被怀疑的疾病基因尚未得到充分认识。因此，虽然HLA分型已被用于检测无症状的患病同胞，但尚未应用于其他亲属。我们提出一种方法，其中使用贝叶斯法则来计算配偶带入家族的指定HLA标记单倍型携带血色素沉着症基因的概率。A3、B14和A3、B7单倍型就是这样的高风险标记。当这些单倍型从未患病的父母遗传而来时，血色素沉着症患者的后代患该病的风险显著增加。然而，当HLA标记单倍型中不存在A3和B14时，携带血色素沉着症基因的风险低于一般人群。这种方法有助于识别患该病风险较高的家庭成员，然后这些成员可接受适当的定期筛查。
