Characterising gene expression diversity in Indonesia

© 2021 Katalina BobowikGenomic studies are disproportionately composed of populations of European ancestry. Given the diverse demographic history of modern humans, this fails to capture the full landscape of human genetic variation. In turn, this has implications for understanding complex disease and accurately assessing disease risk across a diverse range of populations. Indonesia, the world’s fourth largest country by population, is a country that is incredibly ethnically diversity, yet is severely underrepresented in genomic studies. Because of this lack of diversity, this thesis utilises whole blood transcriptomes---a molecular phenotype which can provide information about the activity of a cell and its response to the environment---from three remote island populations spanning the genomic and geographical axes of the country. In the first part of this thesis, I characterise whole blood transcriptomes of these remote populations and investigate contributions of ancestry on molecular phenotypic patterns. The second part of this thesis characterises the ways that these populations respond to their environment, in particular to pathogens in the region. I do this first by investing the effects of malaria, a disease estimated to infect 2.5 million people every year in Indonesia, on Plasmodium-infected individuals. Due to the high pathogenic diversity within the country, I also identify other pathogens within whole blood transcriptomes and explore how they influence human blood expression profiles. By doing so, I find that there are island-level differences correlating with geography, with individuals of Papuan ancestry being most distinct from populations of Asian ancestry. I also find that environmental variables are important contributors to molecular phenotypes, with malaria and flavivirus having clear contributions to shaping the immune response. By characterising molecular phenotypes across Indonesia, this study provides a valuable step in understanding human genetic diversity and genome function outside of populations of European ancestry. It also adds to ongoing literature about how populations differ in their response to disease, ultimately aiding in better diagnostics and therapeutics