Browsing by Author "Rugamika, Emile Chimusa"

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    Genetic dating and pattern of admixture in modern human evolution
    (2017) Defo, Joel; Mulder, Nicola; Rugamika, Emile Chimusa
    Genetic variation is shaped by admixture between populations in an evolutionary process. The mixture dynamic between groups of populations results in a mosaic of chromosomal segments inherited from multiple ancestral populations. The distribution of ancestral chromosomal segments and the recombination breakpoints in an admixed genome provide information about the time of admixture. Studying populations with particular ancestries has become a major interest in population genetics because of medical and evolutionary impacts of the patterns of single nucleotide polymorphisms. It provides a better understanding of the impact of population migrations and helps us uncover interactions between several populations. Most of the research on admixed population dating has focused on a single interaction between two populations using various approaches. Some have extended this to mixing of three populations based on assumptions and approaches which differ from one tool to another. However, the inference of distinct ancestral proportions along the genome of an admixed individual and plausible dates of admixture, still remain a challenge in the case of multi-way admixed populations. This dissertation consists of three research initiatives. First, provide a succinct review of current methods for dating the admixture events. We accomplish this by providing a comprehensive review and comparison of current methods pertinent to date admixture event. Second, we assess various admixture dating tools which estimate the time of admixture between two parental populations. We do so by performing various simulations assuming a particular number of generations and use these to evaluate the tools. Third, we apply the top three assessed methods to some admixed populations from the 1000 Genomes project. Despite MALDER shows improvement and produces reasonable date estimates over other current methods, the results from both simulation and real data suggest that dating ancient admixture events accounting for the effect of other admixtures remains a challenge. Our results suggest the need for developing a new approach to date ancient and complex admixture events in multi-way admixed populations.
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    Mapping genes underlying ethnic differences in tuberculosis risk by linkage disequilibrium in the South African coloured population of the Western Cape
    (2013) Rugamika, Emile Chimusa; Mulder, Nicola; Price, Alkes; Van Helden, Eileen Hoal
    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.