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One of the biggest projects ever undertaken to identify genetic variants that predispose some people to certain diseases was begun in 2005, thanks to £9 million funding from the Wellcome Trust. The ground-breaking results of this study were published in June this year.

It is an excellent illustration of the importance of knowing the human genome sequence and cataloguing its variations. Hopefully, with the insight gained into these diseases we will be able to make real progress in combating them.

Dr Mark Walport, Director of the Wellcome Trust

The Wellcome Trust Case Control Consortium (WTCCC) brought together 50 research groups from dozens of institutions in the UK, including the Wellcome Trust Sanger Institute at Hinxton, Cambridge, and the University of Cambridge. The success of the project depended both on capitalising on the knowledge built by the Human Genome Project and the HapMap Project, two consortia in which the Sanger Institute was a major partner, and also on the sheer size of the collaboration across the UK.

Dr Panos Deloukas, who led the team at the Sanger Institute, explains: ‘This was unprecedented in the UK. The sharing of samples and data on this scale has changed the ethos of the research community – through working with 50 laboratories across the country and conducting large-scale disease genetics at a level that has never been done before.’

The collaborators contributed their large national collections of DNA samples collected from different patient groups – totalling an incredible 17,000 samples across the UK (2000 patients for each of the diseases studied plus 3000 healthy controls) – allowing over 10 billion pieces of genetic information to be analysed by genome scan using the Affymetrix GeneChip assay. Tiny genetic variations between individuals that predispose to type 1 and type 2 diabetes, Crohn’s disease, bipolar disorder, coronary heart disease, hypertension and rheumatoid arthritis were sought. By identifying these ‘genetic signposts’, scientists might understand which people are most at risk and why.

‘We have found 24 genomic regions with very strong evidence of harbouring variants that underlie six of the phenotypes we studied and we saw a spectrum of genetic architectures among these common diseases,’ explains Dr Deloukas. ‘Once we had these findings then the medical collaborators provided insight into the significance of the gene associations and tried to replicate them.’

Significant new breakthroughs have been made for Crohn’s disease and type 1 diabetes, and a link between the two diseases has been discovered. Dr Miles Parkes (Gastroenterology Unit, Addenbrooke’s Hospital, Cambridge) and Professor John Todd (Department of Medical Genetics, University of Cambridge), both participants in the WTCCC, are now leading studies to follow up these findings. ‘It’s rewarding to see that the highly significant genetic associations are now being replicated in independent samples,’ says Dr Deloukas. ‘The framework set up by the WTCCC clearly works.’

Dr Mark Walport, Director of the Wellcome Trust, views the WTCCC as a success: ‘It is an excellent illustration of the importance of knowing the human genome sequence and cataloguing its variations. Hopefully, with the insight gained into these diseases we will be able to make real progress in combating them.’

For more information on the Wellcome Trust Sanger Institute and the WTCCC (including a full list of participants), please go to and

The Wellcome Trust

<div> <p>The Wellcome Trust is well known as the leading funder of biomedical research in the UK, spending many millions on major research projects that have tangible impacts on health and disease.</p> <p>This ethos is abundantly evident in the £9 million support given to the Wellcome Trust Case Control Consortium, a collaboration of leading human geneticists across the UK, to analyse thousands of DNA samples and identify genetic predispositions to common diseases. The Trust also embraces studies on how biomedical research affects people and society; the funding of a research project being undertaken in the University of Cambridge’s Centre for Family Research is an example of this rounded view.</p> <p>The Wellcome Trust is the UK’s largest source of funds for biomedical research and the second largest medical research charity in the world. Spending around £500 million each year in the UK and internationally, the mission of the Trust is to support the brightest scientists with the best ideas, and to ‘respond flexibly to medical needs and scientific opportunities’. Through support of a broad portfolio of biomedical research from immunology and infectious diseases to physiological sciences, the Trust aims to make a difference by advancing understanding of the processes that underpin health and disease. And, as the leading funder of translation research in the UK, the Trust is also committed to translating research innovations into health benefits. Technology Transfer at the Trust can help bridge the gap between fundamental research and commercial application by funding research that is sometimes deemed ‘too early’ or ‘too high-risk’ to be pursued by the corporate healthcare or investment sectors.</p> <p>Perhaps less well known are the Trust’s funding streams across medical humanities and public engagement. Through these, the importance is recognised of engaging with society to foster an informed climate within which biomedical research can flourish. This understanding can inform many things, from the ethical conduct of research, to the development of public policy and regulatory environments, to the enlightened debate about biomedical science, its achievements, applications and implications.</p> </div>

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