HLA-linked genetic control of host response to Mycobacterium leprae

Non-random parental HLA-haplotype segregation is demonstrated in siblings with leprosy. A new method is described for the statistical analysis of non-random segregation among sibships of different sizes. Sibs with the same type of leprosy show a significant excess of identical HLA haplotypes. This is also true for families in which only tuberculoid leprosy is found, which is by far the commonest type in the population studied. However, sibs affected with different types of leprosy share a haplotype less often than expected. This indicates that both susceptibility to and type of leprosy are controlled by at least two HLA-linked genes. Our findings suggest that the equivocal results of previous population studies are due to differences of linkage disequilibrium between HLA-linked genes controlling the host response to Mycobacterium leprae and alleles of HLA A and B loci in various populations.