SUSCEPTIBILITY TO LEPROSY IS LINKED TO THE HUMAN NRAMP1 GENE

Leprosy is a debilitating infectious disease of human skin and nerves, Genetic factors of the host play an important role in the manifestati on of disease susceptibility, The human NRAMP1 gene is a leprosy susce ptibility candidate locus since its murine homologue Nramp1 (formerly Lsh/Ity/Bcg) controls innate resistance to Mycobacterium lepraemurium. In this study, 168 members of 20 multiplex leprosy families were geno typed for NRAMP1 alleles and 4 closely linked polymorphic markers, Hig hly informative haplotypes overlapping the NRAMP1 gene were constructe d, and the haplotype segregation into leprosy-affected offspring was a nalyzed. It was observed that the segregation of NRAMP1 haplotypes int o affected siblings was significantly nonrandom, This finding is consi stent with the hypothesis that NRAMP1 itself is a leprosy susceptibili ty locus.