Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania

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The risk and prognosis of tuberculosis (TB) are affected by both human and bacterial genetic factors. To identify interacting human and bacterial genetic loci, we leveraged paired human and Mycobacterium tuberculosis ( M . tb ) genomic data from 1000 Tanzanian TB patients. Through a genome-to-genome approach, we identified two pairs of human and M . tb genetic variants that are significantly associated. One of the human genetic variants maps to the intron of PRDM15 , a gene involved in apoptosis regulation. The other human variant maps to an intergenic region close to TIMM21 and FBXO15 . In addition, we observed that a group of linked M . tb epitope variants were significantly associated with HLA-DRB1 variation. This suggests that even though epitope variation is rare in M . tb in general, specific epitopes might still be under immune selective pressure. Overall, our study pinpoints sites of genomic conflicts between humans and M . tb , suggesting bacterial escape from host selection pressure.

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