Population and molecular genetics of susceptibility to intracellular pathogens

Abstract

In the mouse, innate resistance to infection with certain species of Mycobacteria, Salmonella typhimurium and Leishmania donovani is controlled by the expression of a single dominant chromosome 1 gene, designated Bcg. The major effect of the Beg locus is the modulation of the growth rate of these pathogens in cells of the reticuloendothelial tissues during early infection. Using a positional cloning approach, a novel gene designated Nramp has recently been identified as a candidate gene for Bcg. Comparison of linkage and physical maps of mouse, human, bovine and chicken chromosomes indicates that a large cluster of genes in the proximal portion of mouse chromosome 1 is conserved among a variety of species. This has opened up the possibilities of testing the candidacy of Nramp for host resistance and susceptibility to human tuberculosis and leprosy, chicken salmonellosis and cow brucellosis.