International Consortium Completes Map Of Human Genetic Variation

In the report, published in Nature (27 October 2005), more than 200 researchers from Canada, China, Japan, Nigeria, the United Kingdom and the United States describe the initial results from their three-year public–private effort to chart the patterns of genetic variation that are common in the world’s population. Their findings show that the search for clinically relevant genes can be simplified by using the map of variation developed by the HapMap Project.

Much of our genetic variation is caused by single-nucleotide differences in our DNA code: these are called single nucleotide polymorphisms, or SNPs. As a result, each of us has a unique genetic code that typically differs in about 3 million nucleotides from every other person

The HapMap project has shown patterns of association between SNPs studied in different populations from around the world. These can be used to simplify studies to understand how genetic variation contributes to health and disease.

“Humans are genetically 99.9% identical: it is the tiny percentage that is different that holds the key to why some of us are more susceptible to common diseases such as diabetes and hypertension or respond differently to treatment with certain drugs,” said Dr Panos Deloukas, Senior Investigator, Division of Medical Genetics, the Wellcome Trust Sanger Institute. “It has been both fascinating and rewarding to be part of this collaborative enterprise that has already mapped one million SNPs and will shortly add another two million to the map.”

“The Wellcome Trust Sanger Institute has played a key role in generating a comprehensive list of common variants and in developing the HapMap. The Phase I map reported here has already become an indispensable tool for researchers hunting the genetic components of disease. The Phase II map will offer even greater power to detect such functionally important genetic changes.”

“This report describes a remarkable step in our journey to understand human biology and disease,” explained Professor Peter Donnelly, Department of Statistics, University of Oxford and one of two corresponding authors on the report. “The human genome sequence provided us with the list of many of the parts to make a human. The HapMap provides us with indicators – like Post-It notes – which we can focus on in looking for genes involved in common disease.

“The HapMap also provides unparalleled information about the targets of natural selection in the genome, and about the process of recombination, by which DNA from both our parents is combined and shuffled when we pass it on to our children.”

Medical genetics will benefit enormously from the increased power that the HapMap provides. By using HapMap data to compare the SNP patterns of people affected by a disease with those of unaffected people, researchers can survey the whole genome and identify genetic contributions to common diseases more efficiently than has been possible without this genome-wide map of variation: the HapMap Project has simplified the search for gene variants as much as20-fold.

The publicly available SNP datasets were used by medical researchers even before the first draft of the map was completed. For example, in March 2005, studies published in the journal Science used HapMap data to uncover a genetic variation that substantially increases the risk of age-related macular degeneration, the leading cause of severe vision loss in the elderly.

Many other discoveries lie on the horizon as the HapMap simplifies studies of other common diseases: more than 70 papers and presentations related to the HapMap are on the programme for the current meeting of the American Society of Human Genetics in Salt Lake City, Utah.

“The HapMap is a remarkable resource that will accelerate the search for genes involved in common ailments, such as heart disease and obesity”, said Dr Mark Walport, Director of the Wellcome Trust. “It is freely available to researchers around the globe and is already being exploited to answer important questions about health and disease.

“The HapMap is an excellent example of how the combination of public and private funds can be an extremely effective and efficient means of establishing large-scale biomedical resources.

“The Wellcome Trust is delighted to be a part of the HapMap, by supporting the significant contributions of the Wellcome Trust Sanger Institute and the Wellcome Trust Centre for Human Genetics, Oxford.”

The Wellcome Trust recently announced funding of £9M for research to identify the genetic variations that may predispose people to or protect them from eight major diseases. In the Wellcome Trust Case Control Consortium (WTCCC), 24 leading human geneticists will analyse thousands of DNA samples from patients suffering with different diseases to identify common genetic variations for each condition. By identifying these genetic signposts, researchers expect to be able to understand which people are most at risk, and also produce more effective treatments.

“The Case Control Consortium is making full use of the HapMap in its efforts to identify genes that are implicated in eight common diseases: tuberculosis, coronary heart disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Crohn's disease, bipolar disorder and hypertension,” explained Professor Donnelly.

“These are not simple challenges but the combination of resources developed through the two initiatives will undoubtedly speed our understanding of these diseases and accelerate the discovery of new diagnostics and treatments.”