A major susceptibility locus for leprosy in India maps to chromosome 10p13

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, is pr evalent in India, where about half of the world's estimated 800,000 cases o ccur(1). A role for the genetics of the host in variable susceptibility to leprosy has been indicated by familial clustering, twin studies, complex se gregation analyses and human leukocyte antigen (HLA) association studies. W e report here a genetic linkage scan of the genomes of 224 families from So uth India, containing 245 independent affected sibpairs with leprosy, mainl y of the paucibacillary type. In a two-stage genome screen using 396 micros atellite markers, we found significant linkage (maximum lod score (MLS)=4.0 9, P<2x10(-5)) on chromosome 10p13 for a series of neighboring microsatelli te markers, providing evidence for a major locus for this prevalent infecti ous disease. Thus, despite the polygenic nature of infectious disease susce ptibility, some major, non-HLA-linked loci exist that may be mapped through obtainable numbers of affected sibling pairs.