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dc.contributor.authorNakabuye, Hellen
dc.date.accessioned2022-12-21T11:10:58Z
dc.date.available2022-12-21T11:10:58Z
dc.date.issued2022-08-19
dc.identifier.citationNakabuye, H(2022) Insights into genomic variations between Mycobacterium tuberculosis compartmentalized in the lungs and blood of HIV-infected individuals in Uganda(Unpublished Masters Dissertation) Makerere University Kampalaen_US
dc.identifier.urihttp://hdl.handle.net/10570/11217
dc.descriptionA Research Dissertation submitted to the Directorate of Research and Graduate Training as a requirement in partial fulfillment for the award of Master of Science in Bioinformatics degree of Makerere Universityen_US
dc.description.abstractIntroduction: Mycobacterium tuberculosis (MTB), particularly clinical strains present a genomic diversity that ranges from several single nucleotide polymorphisms (SNPs) to insertions and deletions (INDELS). This study assessed the genetic variations between sequences of isolates belonging to the MTB Uganda family, a sub-lineage of the MTB lineage 4, from the lungs and blood of TB-HIV positive individuals in Uganda with the hypothesis that sequences of isolates from the blood have unique SNPs and INDELs that characterize MTB survival. Methods: A case-control study was conducted in-silico. Twenty-four MTB blood and lung sequences were examined in this study. The sequences were aligned against the H37Rv (RefSeq: NC_000962.3) reference genome using BWA-MEM. The alignment quality was checked using IGV. SAMtools was used to sort and index the alignment⁠. FreeBayes was used to identify SNPs and INDELs. The SNPs and INDELs were annotated using SnpEff. The 'cat' and 'grep' commands were used to compare and analyze variants between the MTB blood and lung sequences, and then the functions of the genes in which the variants unique to the blood sequences occurred were identified. Results: Comparative analysis of the genetic variation of the samples showed that MTB blood isolates had 11 virulence genes with distinctive non-synonymous SNPs, which were absent in MTB lung isolates. The majority of the INDELs were found in non-virulence genes, with the remainder found in both blood and lung isolate sequences. Discussion: Overall, the 11 virulence genes identified in this study that had distinctive non synonymous SNPs are implicated in pathways that increase CFUs in the lungs and organs, as well as lower host survival, increase host tissue damage, and enhance tissue pathology, allowing for human host persistence. The true role of all SNPs mentioned in this study is difficult to determine. ix This supports the theory that MTB-blood isolates have SNPs that let them survive longer than MTB-pulmonary isolates, allowing these strains to stay in the blood of their hosts. Conclusions: MTB blood sequences have distinctive SNPs, which could explain the capacity of MTB blood isolates to persist outside of the lungs (in blood) of HIV-infected individualsen_US
dc.description.sponsorshipBreCA Mapronano ACEen_US
dc.language.isoenen_US
dc.publisherMakerere Universityen_US
dc.subjectcompartmentalizeden_US
dc.subjectMycobacterium tuberculosisen_US
dc.subjectGenomic variationsen_US
dc.titleInsights into genomic variations between Mycobacterium tuberculosis compartmentalized in the lungs and blood of HIV-infected individuals in Ugandaen_US
dc.typeThesisen_US


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