Leveraging genetic variation to understand chromosome pairing, meiosis and the evolution of human disease risk

In healthy reproduction, producing sperm and eggs (meiosis) requires our paternal and maternal chromosomes to pair (synapse) and swap DNA (recombine). Errors in this process are responsible for a range of human diseases. It has been unknown how chromosomes pair, but we have shown how a gene called PRDM9 aids this process. 

We will perform experiments to understand how synapsis succeeds or fails depending on how PRDM9 binds. We will examine single cells to explore how the binding of many proteins, including PRDM9, coordinates meiosis. Recombination means the evolutionary trees that link related people have variations along the genome. We will extend our previous work on human migrations and develop new approaches to identify hidden evolutionary trees for thousands of people and for different species. This will help us define whether mutations that affect the risk of disease are mainly young or ancient and how this reflects natural selection.