We propose to extend an existing collection of DNA extracts from TB patients and their corresponding TB DNA to establish the world’s largest resource of extracts from a population of TB patients and 5000 ethnically matched healthly controls. The bank will comprise 5000 DNA host DNA extracts paired the DNA and cultures of the strain of Mycobacterium tuberculosis causing their disease. We will perform a genome-wide scan to discover human genes predisposing to TB. We will then localise causal variants and study their role in a case-control population TB sample from another high incidence country in Africa ,Ghana. We will extensively characterise TB strains from a population in Russia using spoligotyping, minisatellite analysis, and SNP analysis of genes putatively associated with virulence and analyse the host-pathogen interaction identifying mycobacterial genes affecting the course of TB, the innate response to TB and outcome at a genetic level. Based on the existing collection of matched host-pathogen DNA we will perform functional experiments of the role of identified mycobacterial factors such as PE variants and the effect of this variation on aspects of innate immunity as influenced by newly-identified TB-associated genes.
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