School of BioSciences - Theses
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ItemGenetic Variation Within an Indigenous Australian Cohort and its Implications for Future Studies of Genomics, Health and Disease( 2022)Gaining an understanding of the genetic characteristics of human populations is important for establishing approaches to and expectations from future studies of genomics, health and disease involving these groups. While genomic studies have recently expanded in scope to sample from a wide range of human ancestry groups, the Indigenous communities of Australia remain poorly characterised, and under-represented in global reference panels. Our failure to gain an understanding of patterns of genetic variation within these communities, and how they differ from other human groups, may widen the already considerable gap in health outcomes between Indigenous Australians and the general Australian population. To address this issue, the National Centre for Indigenous Genomics (NCIG) has collected genomic data from four Indigenous Australian communities from across a wide expanse of the continent. This thesis will describe the analysis of the patterns of genetic variation and diversity within this dataset, and will emphasise how they underpin future research of genomics, health and disease for Indigenous Australians. Firstly, this thesis will describe various forms of analysis aiming to identify the source and quantify the degree of non-Indigenous admixture within the NCIG dataset, and detail approaches to ‘mask’ these regions, and analyse exclusively the Indigenous component of each genome. After producing this masked dataset, subsequent analysis will explore various aspects of Indigenous Australian population variation and diversity relevant to future studies of genomics, health and disease. In particular, it will explore patterns of ‘population structure’ within Indigenous Australian groups, and compare these to patterns observed within human cohorts separated by comparable distances within other regions of the world. The medical and genomic implications of the immense degree of structure, haplotype and rare allele sharing within the Indigenous Australian communities will then be discussed. Subsequently, this thesis will analyse Indigenous Australian genomic variation within the context of worldwide human populations. By analysing the NCIG dataset alongside a diverse global cohort, this investigation will show the high abundance of novel genetic variation within these communities, and will emphasise additional genetic characteristics relevant to the design of future studies involving Indigenous Australian genomes. More demographically oriented analysis, involving Indigenous Australian communities, and groups from the surrounding Oceanic region, will provide context for the key findings presented within this thesis. This data will reveal a previously undocumented history of genetic interaction between the populations of Melanesia and northern Australia, and will show Indigenous Australian communities to have sustained small, yet stable population sizes over recent millennia. This thesis will close with an analysis of patterns of uniparental genetic variation within the dataset, and will assess the ways this data supports autosomal based inferences. In particular, this chapter will highlight the presence of a globally rare, and presumably deleterious Y-chromosome variant, which is present at near fixation within the Tiwi Island community.