Ancient genomics and the Atlantic burden (360G-Wellcome-205072_Z_16_Z)

Massive human genome resequencing projects are in train to further the understanding of the genetic contributions to disease. However these offer a limited view of genome genealogies, variant history and past selection, all of which are instrument to the models underpinning genomic epidemiology. There is a need to add a temporal dimension with ancient genomes of similar quality. The Atlantic edge populations are termini for successive prehistoric range expansions, have particular disease burdens and wide diasporic impact and are thus a compelling target for such. This project will sequence 160 ancient Irish, Portuguese and other genomes sampled throughout prehistory to 15X coverage. Importantly, whole genome sequencing will allow the interrogation of all potentially functional genomic elements without ascertainment bias. Coding, non-coding and copy number variant trajectories will be combined with a realistically modeled demographic prehistory to gauge the interplay of drift and selection acting on putatively deleterious, advantageous, complex trait associated and Mendelian disease polymorphisms. This will identify the origins of the Atlantic disease burden, help model the genetic architecture of complex traits, aid in interpretation of disease resequencing studies and test specific hypotheses about prehistory.