Genes and Genetics of Tuberculosis

Tuberculosis affects human life globally for long time. About one third of the world’s population is infected with the causal pathogen Mycobacterium tuberculosis but without presenting any clinical symptoms. The difference in clinical outcome of infection suggests that host genetic makeup is responsible for such variability. Attempts have been made to identify the underlying genes. In case of Mendelian susceptibility to mycobacterial disease (MSMD) a rare disease with immune-deficiency, mutations were identified in genes that impair IFN γ signaling pathway. Linkage studies have identified several loci but exact gene was never pinpointed. Candidate gene association studies carried out in different populations, identified several risk alleles. But findings of all these studies were hardly replicated in another population. Findings are also not justifiable in some cases because of limited sample size. GWAS also identified several susceptible locus, many of which were replicated in another population where as many were not. Gene expression analysis also adds onto identification of gene implicated in infection and thus enhances knowledge on genes playing significant role in mycobacterium infection. However all these studies show that not a single gene but many genes are orchestrated together in determining the fate of infection. More research is necessary to find out such genes, their interaction with other members and complicated network formed.