Poster Presentation 40th Annual Lorne Genome Conference 2019

Characterising functional genetic variation in Island Southeast Asia (#158)

Irene Gallego Romero 1
  1. University of Melbourne, Parkville, VIC, Australia

Studies of gene regulatory function in the human genome have been largely centred on populations of European ancestry. This approach does not capture the wealth of existing genetic diversity in humans today, and has negatively impacted our ability to predict complex phenotypes in people of other ethnic backgrounds - eg, reported biases in polygenic risk score prediction, or in the inter-population portability of GWAS hits. To begin redressing this disparity, and to better our understanding of the dynamics of the peopling of Island Southeast Asia, we have generated whole genome sequencing (30x coverage), RNA sequencing (30 million read pairs from whole blood) and DNA methylation (800,000 sites genome-wide from whole blood) data from over 100 individuals practicing traditional lifestyles in three distinct islands in Indonesia. Our dataset captures the two main sources of ancestry in the region - Papuan ancestry derived from the original settlers of the region roughly 50,000 years ago, and much more recent gene flow from Neolithic Austronesian farmers. We identify over 2000 differentially expressed genes between the islands, with an excess of genes impacting immune function. Additionally, our dataset allows us to address questions about on the functional significance of introgression from our mysterious ancestors, the Denisovans,  to these populations and to compare expression QTL maps established from Indonesian individuals to existing ones built from European populations.