Recombination; statistical genetics; genomic epidemiology; genomics
We are interested in understanding the impact of recombination in shaping natural diversity and evolution. We are also interested in understanding the mechanisms promoting and regulating recombination in mammals.
The Donnelly group, in collaboration with others, has developed and applied cutting-edge statistical methods that utilize genome-wide variation data to detect and characterise human population structure and admixture.
We have developed new methods for investigating the role of genetics and environment in human health.
In collaboration with the Myers group, we identified the role of PRDM9 in marking recombination hotspots, and the impact of PRDM9's own evolution and diversity. Our recent work on the role of PRDM9 in hybrid infertility in mice brought together these strands by showing how the evolution of the genome, as a consequence of PRDM9's role in marking recombination initiation, can lead to speciation.
The demographic history of human populations leaves particular signatures in the DNA of modern-day descendants. The large amounts of genome-wide genetic data that can now be collected provide opportunities to study human history from an angle that has never been possible before.
Findings from the Donnelly group’s research to use genetic data to detect and characterise human population structure and admixture have proven to align well with the historical record, as well as provided new insights into the impact of historical demographic events on the general population.
Recent applications include the study of population structure and history of migration and settlement in the British Isles. This study is the largest and most comprehensive of its kind in Britain, and revealed “a rich and detailed pattern of genetic differentiation with remarkable concordance between genetic clusters and geography.” The findings of this research formed the basis of a unique exhibition at the Museum of Natural History, Oxford, which brings the genetic story of Britain to the public. http://www.oum.ox.ac.uk/settlers/
The group has used a similar approach to detect population structure at ultra-fine geographic scales (<10Km) in Spain; and quantified the genetic impact of major historical events in the region, including the migration of people of north-west African origin subsequent to the Muslim conquest of Iberia in 711CE.
We have collaborated with UK Biobank on genotype analysis of 500,000 volunteers who have contributed physical measurements and information about their health and lifestyle. We have developed methods for discovering genetic variants that have effects on the variance of the phenotype, in contrast to most genetic association studies that focus on finding genetic variants that affect the mean level of a trait. This has involved developing both novel theory, computation techniques, and software (https://github.com/AlexTISYoung/hlmm). Genetic effects on phenotypic variability can be the result of gene-by-environment interactions, and we have used our approach to identify novel interactions between genetic and environmental factors affecting human health.