We have continued our gene to phenotype studies in type 1 diabetes with several publications this year relating T1D-associated genotypes with phenotypes of immune cells in blood samples and purified immune cells. We have evidence the plasma protein soluble CD25 may be a biomarker of early diagnosis of T1D; and that increased type 1 interferon production is associated with increased susceptibility to type 1 diabetes, by inheriting alleles of genes that promote this pathway and by viral infections (published in Nature). This information will underpin the identification of disease mechanisms that could be targets for therapeutic interventions.
A continuing strategic development has been major continued efforts in the Cambridge BioResource. This year we have enrolled a further 3,800 local volunteers onto the BioResource panel bringing the total now to over 9,500 volunteers and over 400 existing CBR volunteers have participated in Phase 2 research studies. Individuals from the Cambridge, and now, wider regions, who have volunteered to participate in this resource, have provided samples for DNA extraction to enable genotyping for (disease-associated) polymorphisms of interest. Individuals can be approached on the basis of their genotype to undertake detailed phenotyping studies, including cellular assays. Samples of DNA, plasma and serum have been deposited in a dedicated biorepository, lifestyle information has been collected and stored in a purpose-designed database, and full blood counts have been determined.
One of the major phase 2 studies, 'An investigation into genes and mechanisms based on genotypephenotype correlations in type 1 diabetes and related diseases using peripheral blood mononuclear cells from volunteers that are part of the Cambridge BioResource' by John Todd and Linda Wicker in the Department of Medical Genetics, continued, in 2009-2010, recruiting 356 subjects for our immunophenotyping studies. A new BRC facility has been set up this year, funded jointly by the NIHR BRC, the University, and an award from the MRC: the Eastern Sequence and Informatics Hub (EASIH; director, John Todd), which in addition to supporting several projects, is developing next generation sequencing in X-linked intellectual disability diagnostic testing, with Lucy Raymond and Howard Martin; and also HLA typing with Cristina Navarrete at the NHS Blood and Transplant at Colindale. Both these projects could have near-term impact on patients.
Core funding for the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory (director, John Todd) for the next five years was renewed recently (£10M). The laboratory has also helped in the establishment of state-of-the-art, cross-campus flow cytometric phenotyping facilities, which are essential in the path from disease susceptibility genes to disease mechanisms and pathways, towards primary prevention of this major disease of childhood and its increasing population incidence.