On the tenth anniversary of the completion of the first draft of the human genome - a draft that took ten years to complete - the Wellcome Trust has launched a project to decode the genomes of 10,000 people over the next three years. This will be one of the largest genome-sequencing programmes ever undertaken and will analyse the genomes of one in 6,000 people in the UK.
The UK10K project is expected to uncover many rare genetic variants that are important in human disease, giving a much deeper picture of genetics that can be applied to other studies, both in the UK and around the world. It is being funded through a £10.5 million Strategic Award to the Wellcome Trust Sanger Institute in collaboration with clinical researchers from around the UK, using samples and cohort data collected over many years.
There are two components to the UK10K project: the genomes of 4,000 people, who have each been studied for many diseases and traits over many years, will be completely sequenced; and the gene-containing regions of the genomes of 6,000 people with extreme obesity, neurodevelopmental disease and other conditions will also be studied.
"Although genetics over the past five years has yielded a rich harvest of hundreds of variants associated with disease, much more remains to be discovered," says Dr Richard Durbin, principal investigator on the project, from the Wellcome Trust Sanger Institute. "With this award, we are seizing the chance to use technological advances in DNA sequencing to find variants that have even greater consequence for health."
The 4,000 whole genomes will be from two important groups of people who have been studied for many years - the TwinsUK and ALSPAC (Avon Longitudinal Study of Parents and Children - also known as Children of the 90s) studies. The first includes 11,000 twins born in the UK, some of whom have taken part in studies for more than 18 years. ALSPAC includes more than 9,000 people originally from Avon in south-west England, followed from birth in 1991-92. The data for each group include extensive descriptions of their health and their development.
Studying this large group will help researchers build a near-complete catalogue of genetic variation in these 4,000 people. The depth of information recorded from them will provide a real opportunity to tie genetic variants to measured health-related differences between individuals. This should help identify the few thousand genetic variants - among the 3 million each of us carries - that are important in disease.
The information gathered from these 4,000 will be strengthened by the second component of 6,000 people, recruited by clinicians, who have a severe condition thought to have a genetic cause. These include severe obesity, autism, schizophrenia and congenital heart disease. The gene-containing regions of these people's genomes - known as 'exomes' - which are likely to include the genetic variants important in their condition, will be analysed using new methods based in part on cutting-edge techniques developed at the Wellcome Trust Sanger Institute.
"We are fortunate in the UK to have such excellent collections of clinical samples provided by volunteers to help research and to help others," says Professor Tim Spector, who leads the TwinsUK study at King's College London. "10,000 volunteers have contributed to this, the largest genome-sequencing project so far undertaken. It's a stunning commentary on the generosity of participants in UK studies."
The researchers point out that the results will have their most immediate impact in genetics, contributing to an ongoing transformation of our understanding of human genetic variation. In some cases this may have direct clinical relevance. But more often it will lead to advances in our understanding of disease biology, which should, in time, reach through to medical applications.
UK10K starts exactly ten years after the draft of the first human reference genome was announced by the Human Genome Project.
Sir Mark Walport, Director of the Wellcome Trust, says: "The pace of technological change is extraordinary. We can now study the genome sequences of 10,000 people in three years. Just a decade ago it took much more time and money to decode just a single sequence. The involvement of clinicians, researchers and, most importantly, the thousands of people who have donated DNA samples, will help us to correlate genetic variation with individual variation in health and disease, and help to deliver on the long-term promise of the Human Genome Project."
The UK10K project was co-developed by Professor Leena Peltonen, former head of Human Genetics at the Wellcome Trust Sanger Institute. Professor Peltonen passed away on 11 March 2010 at her home in Finland after a long battle with cancer.
Dr Durbin says: "This project was co-developed by the amazingly energetic and inspiring Professor Leena Peltonen, who sadly died three months ago. I know Leena saw this project as a major opportunity to translate genomics to medical relevance, and we are excited about the opportunity to deliver a project of which she would be proud."