Genetic Susceptibility to Infection
The Jenner genetics group studies genetic susceptibility to a wide range of infectious diseases. The group is headed by Adrian Hill, Director of the Jenner Institute, who is also Professor of Human Genetics at the Wellcome Trust Centre for Human Genetics. The Centre is located on the Old Road Campus in Headington, next to the Jenner Institute Laboratories. The group has studied genetic susceptibility to bacterial, viral and parasitic diseases in populations from five continents but their largest studies have been of sub-Saharan Africans.
The aim of the group is to identify genes that affect people’s risk of acquiring and dying from major tropical infectious diseases. They have a particular interest in major bacterial diseases in Africa such as tuberculosis and bacterial sepsis, but also study HIV / AIDS in Africans and sepsis, pneumococcal disease and respiratory infections in Europeans. The group uses candidate gene analysis, genome-wide linkage and, recently, genome-wide association approaches to map and identify several important susceptibility genes.
Field site studies in Africa
Studies of twins and adoptees first demonstrated that human genetic differences have a major impact on susceptibility to many infectious diseases. The greatest disease burdens from infectious diseases are found in developing countries, particularly in sub-Saharan Africa. With excellent field site collaborators, the group has studied susceptibility to major infections in several African countries including Kenya, Uganda, Malawi, South Africa, The Gambia, Ghana and Senegal. The Hill Group has identified several genes that regulate immune responsiveness that impact on infectious disease susceptibility including CISH, MAL/TIRAP, TLR1 and HLA variants. Several of these genes appear to affect susceptibility to multiple infectious diseases.
Genome-wide association studies
Recently the group has published a genome-wide association study of tuberculosis in Africa as part of the Wellcome Trust Case Control Consortium and showed that, despite the exceptional genetic diversity and complexity of population structure in this continent, new infectious disease genes could be mapped by this approach. Currently, the group is using a similar approach to map genes affection susceptibility to bacteraemia in a Kenyan population and susceptibility to fatal outcome of sepsis in a large multi-centre study in several European countries.
Translation into vaccine development
These genetic studies provide insights into how people differ in their ability to resist and survive serious infections and help design more effective interventions, such as new vaccines to prevent these diseases. The group works closely with Jenner Institute immunologists and vaccine researchers and have ongoing studies to identify genes that affect how well new vaccines work in different individuals.