Variations in the NRAMP1 Gene and Susceptibility to Tuberculosis in West Africans

Among inbred strains of mice, natural resistance to infection with several intracellular pathogens is controlled by a single dominant gene, designated Bcg (also known as Lsh/Ity ). 1 – 3 Two distinct phenotypes, Bcg s and Bcg r, are associated with susceptibility and resistance, respectively, to the early stage of infection with Mycobacterium bovis (bacille Calmette–Guérin), 3 M. avium complex, 4 M. lepraemurium, 5 Leishmania donovani, 2 , 6 and Salmonella typhimurium. 1 A candidate gene was isolated by positional cloning and designated the natural-resistance–associated macrophage protein 1 gene ( Nramp1 ). 7 Nramp1 is expressed only in reticuloendothelial cells. 7 A single nonconservative amino acid substitution of aspartic acid . . .