Whole genome sequence based analysis of genetic variation and genome evolution (360G-Wellcome-207492_Z_17_Z)

£3,027,662

DNA sequencing is a core technology for modern biomedical science, and our ability to sequence genomes with ease and use that information efficiently is still unfolding. I propose first to build new bioinformatics data structures and software to map sequence data, call genetic variants, and integrate phasing and imputation, scaling to millions of samples with high accuracy and making best use of new long read sequencing technologies. These will be based on sequence variation graphs and haplotype panels over them, effectively exploiting already-discovered genetic variation in the population. Second I will develop new statistical methods to infer the evolutionary history of genome sequences to identify ancestral populations, model gene flow between them, and date and place mutations into them. I will apply these methods to modern and ancient samples to elucidate Eurasian and African human population history. Finally, I will apply these methods to new data I collect from the Lake Malawi adaptive radiation of over 500 species of cichlid fish, to infer the evolutionary relationships in the radiation, test models of speciation, and identify genes involved in cranio-facial adaptation. These studies will empower future use of sequencing data in biomedicine, and advance our understanding of genome structure and evolution.

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Grant Details

Amount Awarded 3027662
Applicant Surname Durbin
Approval Committee Science Interview Panel
Award Date 2017-07-11T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Investigator Award in Science
Internal ID 207492/Z/17/Z
Lead Applicant Prof Richard Durbin
Partnership Value 3027662
Planned Dates: End Date 2024-09-30T00:00:00+00:00
Planned Dates: Start Date 2017-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England