Infection genomics: Nramp1 as a major determinant of natural resistance to intracellular infections.
The scope of the tuberculosis (TB) epidemic in the world today is enormous, with about 30 million active cases. Current research into preventing the spread of TB is focused on development of new drugs to inactivate Mycobacterium tuberculosis, the causative agent of TB, as well as on identifying the critical steps of host defense to infection with Mycobacteria, which might also yield therapeutic targets. Our infection genomics approach toward the latter strategy has been to isolate and characterize a mouse gene, Bcg (Nramp1), which controls natural susceptibility to infection with Mycobacteria, as well as Salmonella and Leishmania. Through comparative genomics, we have identified the homologous human NRAMP1 gene, alleles of which are now being used for tests of linkage with TB and leprosy.
Skamene
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Division of Clinical Immunology and Allergy, Montreal General Hospital, Quebec, Canada. MD88@musica.mcgill.ca
Schurr
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Gros
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D000483:Alleles; D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D004196:Disease Outbreaks; D004198:Disease Susceptibility / Q000276:immunology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D016680:Genome, Bacterial; D015894:Genome, Human; D018503:Genome, Protozoan; D014943:Global Health; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007896:Leishmaniasis / Q000235:genetics / Q000276:immunology; D007917:Leprostatic Agents / Q000627:therapeutic use; D007918:Leprosy / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D008264:Macrophages / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009166:Mycobacterium leprae / Q000187:drug effects / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D000099173:Natural Resistance-associated Macrophage Protein 1
D000995:Antitubercular Agents; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D007917:Leprostatic Agents; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1