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Approved research

Tracing the inheritance of genetic disorders and adaptations from ancestral human populations.

Principal Investigator: Eske Willerslev
Approved Research ID: 58935
Approval date: June 16th 2020

Lay summary

It has long been a mystery as to why modern human populations harbour damaging genetic variants in our gene pool, and why natural selection has not weeded such mutations out over time. A key component to understanding why these persist and where they come from is to answer the question of which ancient human populations they derive from. This is the question that our research aims to answer. We will assign each variant in each individual in the UK Biobank to a best guess of its ancestral population - i.e. where that variant has come from if we follow its route back in time. Once we have done this, we will be able to work out if people with, for example, more hunter-gatherer-derived variants are more likely to develop a specific disease, for example type 2 diabetes. Furthermore, we can ask questions such as whether a specific mutation has a greater effect on an individual if it is derived from a specific population, or if mutations that confer an advantage come from specific populations. The scope of the project will begin with looking at ancient human populations in Europe over the last 10,000 years, with the possibility of including older populations later on. It is expected to take up to three years in duration, as it is in conjunction with the sequencing of hundreds of skeletons from across Europe and Asia in the same time period. This research is valuable both as fundamental scientific research and for more practical applications. In terms of the former, as a proof-of-concept project we aim to establish that these methods work and can be applied more widely temporally and spatially: going further back in time, for example tracing mutations from the earliest human populations in Europe 45,000 years ago, and more widely geographically in other parts of the world. In recent years there has been an explosion of sequencing of ancient human genomes, and this type of methodology is crucial in linking such research to modern human health outcomes. Understanding these questions will reduce the stigma associated with many of these diseases, in particular psychiatric disorders, as we recognise that they were valuable at some point in human evolution. It will also inform population-level and individual risk assessment, diagnosis, and treatment of genetic disorders, as we understand what the sequence of an individual's genome means to their health risks and personalised treatment.