| Summary: | Sub-Saharan Africa is believed to possess more human genetic diversity than any other region of the world, a likely consequence of it being the probable place of origin of anatomically modern man. Despite its evolutionary importance studies into the distribution of this genetic variation have been somewhat limited in comparison to Europe, Asia and the Americas, especially with respect to fine-scale studies that would help elucidate local histories and the consequences of ethnic and linguistic interactions. Another possible consequence of knowledge of genetic diversity is that much information of functionally important genetic variants that are potentially relevant to pharmacogenetic research is not available. This lack of information can add to an already prevalent Eurocentric ascertainment bias in current knowledge of genetic variation, depriving sub-Saharan Africa communities of the potential medical benefits pharmacogenetics has to offer. This thesis describes three case studies that form part of an investigation into human genetic variation in sub-Saharan Africa. Chapter 2 uses sex-specific genetic systems to successfully differentiate between two alternative oral histories of the ethnogenesis of the Nso’ people of Cameroon. Chapter 3 establishes that substantial male and female gene flow has occurred among the peoples of the Cross River region of Nigeria, a region that includes multiple ethnic groups speaking distinct languages that appear to have separated hundreds and thousands of years ago. Chapter 3 demonstrates that the drug metabolising enzyme Flavin-containing Monooxygenase 2, which has been shown to be non-functional in all Europeans and Asian individuals collected to date, has a putative functional allele in approximately one third of sub-Saharan Africans, a finding that may have important implications for therapeutic intervention strategies and xenobiotic exposure. This thesis demonstrates inter alia the value of conducting genetic studies in sub-Saharan Africa using large datasets of well known provenance.
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