Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape

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dc.contributor.advisorMulder, Nicolaen_ZA
dc.contributor.advisorPrice, Alkesen_ZA
dc.contributor.advisorVan Helden, Eileen Hoalen_ZA
dc.contributor.authorRugamika, Emile Chimusaen_ZA
dc.date.accessioned2014-12-31T19:29:46Z
dc.date.available2014-12-31T19:29:46Z
dc.date.issued2013en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractThe South Africa Coloured population of the Western Cape is the result of unions between Europeans, Africans (Bantu and Khoisan), and various other populations (Malaysian or Indonesian descent). The world-wide burden of tuberculosis remains an enormous problem, and is particularly severe in this population. In general, admixed populations that have arisen in historical times can make an important contribution to the discovery of disease susceptibility genes if the parental populations exhibit substantial variation in susceptibility. Despite numerous successful genome-wide association studies, detecting variants that have low disease risk still poses a challenge. Furthermore, admixture association studies for multi-way admixed populations pose constant challenges, including the choice of an accurate ancestral panel to infer ancestry and for imputing missing genotypes to identify possible genetic variants causing susceptibility to disease. This thesis addresses some of these challenges. We first developed PROXYANC, an approach to select the best proxy ancestral populations for admixed populations. From the simulation of a multi-way admixed population, we demonstrated the ability and accuracy of PROXYANC in selecting the best proxy ancestry and illustrated the importance of the choice of ancestries in both estimating admixture proportions and imputing missing genotypes. We applied this approach to the South African Coloured population, to refine both the choice of ancestral populations and their genetic contributions. We also demonstrated that the ancestral allele frequency differences correlated with increased linkage disequilibrium in the SAC, and that the increased LD originates from admixture events rather than population bottlenecks. Secondly, we conducted a study to determine whether ancestry-specific genetic contributions affect tuberculosis risk. We additionally conducted imputation genome-wide association studies and a meta-analysis incorporating previous genome-wide association studies of tuberculosis.en_ZA
dc.identifier.apacitationRugamika, E. C. (2013). <i>Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine. Retrieved from http://hdl.handle.net/11427/10691en_ZA
dc.identifier.chicagocitationRugamika, Emile Chimusa. <i>"Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2013. http://hdl.handle.net/11427/10691en_ZA
dc.identifier.citationRugamika, E. 2013. Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Rugamika, Emile Chimusa AB - The South Africa Coloured population of the Western Cape is the result of unions between Europeans, Africans (Bantu and Khoisan), and various other populations (Malaysian or Indonesian descent). The world-wide burden of tuberculosis remains an enormous problem, and is particularly severe in this population. In general, admixed populations that have arisen in historical times can make an important contribution to the discovery of disease susceptibility genes if the parental populations exhibit substantial variation in susceptibility. Despite numerous successful genome-wide association studies, detecting variants that have low disease risk still poses a challenge. Furthermore, admixture association studies for multi-way admixed populations pose constant challenges, including the choice of an accurate ancestral panel to infer ancestry and for imputing missing genotypes to identify possible genetic variants causing susceptibility to disease. This thesis addresses some of these challenges. We first developed PROXYANC, an approach to select the best proxy ancestral populations for admixed populations. From the simulation of a multi-way admixed population, we demonstrated the ability and accuracy of PROXYANC in selecting the best proxy ancestry and illustrated the importance of the choice of ancestries in both estimating admixture proportions and imputing missing genotypes. We applied this approach to the South African Coloured population, to refine both the choice of ancestral populations and their genetic contributions. We also demonstrated that the ancestral allele frequency differences correlated with increased linkage disequilibrium in the SAC, and that the increased LD originates from admixture events rather than population bottlenecks. Secondly, we conducted a study to determine whether ancestry-specific genetic contributions affect tuberculosis risk. We additionally conducted imputation genome-wide association studies and a meta-analysis incorporating previous genome-wide association studies of tuberculosis. DA - 2013 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2013 T1 - Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape TI - Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape UR - http://hdl.handle.net/11427/10691 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/10691
dc.identifier.vancouvercitationRugamika EC. Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Institute of Infectious Disease and Molecular Medicine, 2013 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/10691en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherComputational Biologyen_ZA
dc.titleMapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Capeen_ZA
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhDen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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