Grant: Operating Grant - PA: Institute of Genetics (Bridge Funding)

Identification of human genes controlling resistance and susceptibility to tuberculosis is crucial to developing new treatments and vaccines as well as preventing transmission. Many genetic studies in tuberculosis have been inconclusive due to small datasets and/or inexact clinical phenotypes. Over the last several years, we have successively targeted three areas to identify genetic risk factors. First, we have built up large family datasets in different endemic areas of disease. Second we have designated for study phenotypes only immune tests that are clinically relevant. Third, we have established robust genome wide methods designed for immunological responses. These resources are now being used to identify genes that impact on the quantity of the anti-mycobacterial immune response. Specifically, the present application will focus on the molecular isolation of gene variants that make a person innately resistant to infection with Mycobacterium tuberculosis. Innate resistance to infection is the holy grail of tuberculosis research since without infection no tuberculosis disease can develop.