Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients

Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients

Bibliographic Details
Main Author: McHenry, Michael Lyon
Language:English
Published: Case Western Reserve University School of Graduate Studies / OhioLINK 2021
Subjects:
Epidemiology
Genetics
Medicine
Tuberculosis
Genetic Epidemiology
Infectious Disease
Evolution
Co-Evolution
Lineage
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=case1623754259445275
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-case16237542594452752021-09-02T05:10:39Z Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients McHenry, Michael Lyon Epidemiology Genetics Medicine Tuberculosis Epidemiology Genetics Genetic Epidemiology Infectious Disease Evolution Co-Evolution Lineage Tuberculosis (TB) is a major public health problem, causing more deaths globally than any other pathogen prior to COVID19. It is also the leading cause of death among people infected with human immunodeficiency virus (HIV). Susceptibility to TB can be influenced by human genetic variation. However, factors underlying variation in TB severity are less well studied. Clinical severity is an important phenotype that encompasses prognosis, patient experience, and risk of mortality. Thus, it is important to study severity, as it can help us better understand patients’ quality of life, disease experience, and to predict survival among TB patients receiving treatment. There is also evidence that MTB genetic variation as delineated by phylogenetic lineage can affect TB disease severity, when considered simultaneously with human genetic variations and the interaction between the two. Many genetic studies of TB stop short of linking these genetic effects to biological function. The proposed study will address these fundamental gaps by 1) studying the genomic underpinnings of active TB severity using a meaningful, replicable, and validated clinical phenotype; 2) demonstrating evidence of co-evolution between humans and MTB on a population level how it affects severity; and 3) bridging the gap between genetic variants and immunological function by studying gene expression in the macrophage response. The overall goal is to examine how genomic variation in humans and MTB impact the immunological response to active TB disease and how this correlates with clinical severity. 2021-09-01 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1623754259445275 http://rave.ohiolink.edu/etdc/view?acc_num=case1623754259445275 restricted--full text unavailable until 2023-08-13 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Epidemiology
Genetics
Medicine
Tuberculosis
Epidemiology
Genetics
Genetic Epidemiology
Infectious Disease
Evolution
Co-Evolution
Lineage
spellingShingle Epidemiology
Genetics
Medicine
Tuberculosis
Epidemiology
Genetics
Genetic Epidemiology
Infectious Disease
Evolution
Co-Evolution
Lineage
McHenry, Michael Lyon
Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients
author McHenry, Michael Lyon
author_facet McHenry, Michael Lyon
author_sort McHenry, Michael Lyon
title Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients
title_short Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients
title_full Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients
title_fullStr Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients
title_full_unstemmed Genomic and Co-Evolutionary Determinants of Clinical Severity in Active Tuberculosis Patients
title_sort genomic and co-evolutionary determinants of clinical severity in active tuberculosis patients
publisher Case Western Reserve University School of Graduate Studies / OhioLINK
publishDate 2021
url http://rave.ohiolink.edu/etdc/view?acc_num=case1623754259445275
work_keys_str_mv AT mchenrymichaellyon genomicandcoevolutionarydeterminantsofclinicalseverityinactivetuberculosispatients
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