Mapping A Road To Understanding Human Health - International HapMap Project Starts the Cartography of Human Genome Variation

Mapping A Road To Understanding Human Health

International HapMap Project Starts the Cartography of Human Genome Variation

The quest to track down genes involved in health and disease and our response to treatments is a long and difficult challenge. Today (18th December 2003), in the journal Nature, the International HapMap Consortium, to which The Wellcome Trust is a major contributor, describes important new tools it will produce to enhance our use of the human genome sequence and to fast-track that quest.

Our individual predisposition to disease and our response to medicines are, in part, encoded within our DNA, in the differences (called single-nucleotide polymorphisms, or SNPs) scattered through our genetic sequence. However, we tend to share regions of SNPs with others, and these regions can be mapped onto the reference genome sequence, one-third of which was produced at the Wellcome Trust Sanger Institute.

Importantly, many regions can be 'tagged' by identifying SNPs that are characteristic of the region. The HapMap Project will define those all-important 'tag' SNPs in multiple populations and the regions of the genome where they are located.

As a result of the HapMap Project, researchers will not have to search through the 10,000,000 SNPs that occur in the human genome, but instead will be able to use the map developed by the Project to obtain as much information using a massively reduced number of SNPs, about 500,000.

Dr Mark Walport, Director of the Wellcome Trust, said: "The Wellcome Trust's funding strategy is about improvement of human health. The HapMap is a very important development following on from the Human Genome Project. It will help researchers to find genes contributing to some of our most important diseases, such as diabetes, heart disease and cancer. It will also help us to understand the variations between our individual responses to drug treatments."

In order to maximize the likelihood of identifying most variation and to identify 'tag' SNPs that are broadly representative of all humans, the HapMap Project will use DNA samples from 270 individuals from populations of Yorubans in Nigeria, Japanese, Han Chinese and US residents with ancestry from northern and western Europe. Patterns of variation will be extracted from study of the SNPs present in each of these individuals. Those patterns will provide a basis on which to find the tag SNPs that most efficiently describe the patterns; these tag SNPs are the major resource of the Project.

In the UK, the Project is funded principally by the Wellcome Trust through The Wellcome Trust Sanger Institute near Cambridge and The Wellcome Trust Centre for Human Genetics in Oxford. In addition the Department of Statistics at the University of Oxford leads one of the analysis groups. In all, Trust-funded research will contribute towards 40% of the research effort.

Dr David Bentley, Head of Genetics at the Wellcome Trust Sanger Institute, said: "The HapMap will be applicable to many medical conditions that have a genetic component, especially our common diseases. It is vital that such a resource is readily available. It will be the index of human variation for many years to come."

"The groups contributing to this international Project will release the data and the resulting map of variation as a freely available public resource. In that way, we anticipate maximum medical benefit will accrue in the most rapid fashion."

The HapMap Project is an international collaboration involving researchers in Canada, China, Japan, Nigeria, UK and USA. The results generated will be applicable to all human populations, and will be valuable to researchers around the world.

The US$120M Project was officially announced in October 2002 and is expected to take three years to complete.

Since the announcement of the Project, samples have been obtained and substantial amounts of variation data have already been released. Preliminary analyses of these data support the validity and usefulness of the HapMap.

Today's publication in Nature describes in detail the project's scientific goals and methods.