HARVARD GAZETTE ARCHIVES

All these studies are grounded in data presented in a significant paper published in the Oct. 27 issue of the journal Nature by an international consortium of more than 200 researchers from Canada, China, Japan, Nigeria, the United Kingdom, and the United States. In this paper, the authors describe the patterns of genetic variation in hundreds of human DNA samples collected from four sites around the world.

Perhaps the most striking finding in this mountain of data is the overwhelming evidence for previous work that suggested that human genetic variants located physically close to each other in the genome are collectively inherited as groups, or "haplotypes." The implications - and potential value - of the genome's haplotype structure for medicine has only begun to be realized.

"Built upon the foundation laid by the human genome sequence, the HapMap is a powerful new tool for exploring the root causes of common diseases. We absolutely require such a resource so that we can develop new and much-needed approaches to understand these diseases, such as diabetes, bipolar disorder, cancer, and many others," said David Altshuler, director of the program in Medical and Population Genetics of the Broad Institute of Harvard and MIT and associate professor of genetics and of medicine at Massachusetts General Hospital and Harvard Medical School. Altshuler and Peter Donnelly, of the University of Oxford in England, are the corresponding authors of the Nature paper.

Diseases run in families, and perhaps half the risk of any given common disease can be explained by genetic differences inherited from one's parents. Inheritance also plays a role in the different responses to a drug or to an environmental factor seen in some people. But the underlying causes of these common diseases and therapeutic responses have been largely unknown for reasons that include technological limitations evaluating the range of genetic contributions to disease across many different individuals or populations.

To address this fundamental biomedical research need, a new genomics-based approach to human genetics was proposed nearly a decade ago: to comprehensively catalog common human DNA sequence variations, and to test them systematically for their association to disease. The HapMap is the successful outcome of this proposal.

"The data from the HapMap project allows scientists to select the particular DNA variants that provide the greatest information in the most efficient manner, lowering the costs and increasing the power of genetic research," said Mark Daly, assistant professor in the Center for Human Genetic Research at Massachusetts General Hospital and an associate member of the Broad Institute of Harvard and MIT. Daly led the Boston team's statistical and analytical work and was a member of the writing group for the Nature paper.