Scientists Make New Gene Map

An international team of researchers including Harvard scientists published last week a catalog of common human genetic variants—known as the HapMap—that they hope will lead to a better understanding of the causes of genetically-based diseases such as diabetes, multiple sclerosis, and bipolar disorder.

Harvard researchers from the Broad Institute joined a team of 200 researchers in six nations to complete the $138 million project. Findings from the HapMap, compiled by analyzing genetic data from four ethnic groups—Europeans, Japanese, Chinese, and the Yoruba of Nigeria—were published in last week’s edition of the journal Nature. Researchers found over three million common variants in the three-billion-unit human genome.

Researchers are now planning to use the HapMap data to search for links between common variants and genetically-based diseases.

“What motivates this work is that as medical researchers we understand our knowledge of the causes of prominent diseases is incredibly poor,” said David M. Altshuler, director of the program in medical and population genetics of the Broad Institute. “If you asked me to explain why one person gets diabetes and one does not, we essentially have no idea. We don’t even know what organ is responsible.”

Altshuler and his colleagues are embarking on a study of 3,000 patients during the next 12 months to try to identify which genes contribute to a risk of diabetes.

Pamela B. Sklar, an assistant professor of psychiatry at Harvard Medical School and an associate member of the Broad Institute, is beginning a study of bipolar disorder.

“Since so little is known about bipolar disorder,” she said, “any clue that we would get to a gene [linked to the disorder] could lead us to information that could lead us to discover remedies.”

The variants associated with bipolar disorder will not definitively indicate that someone will have the disease, she said, but will signal an increased risk for the disorder, much like high cholesterol indicates an elevated risk for heart disease.

Diabetes and bipolar disorder are only two of the diseases being studied. In the Boston area alone, researchers are using similar genetic methods to learn more about autism, multiple sclerosis, and heart disease, Altshuler said.

Altshuler said it remains unclear how fruitful this approach to studying disease will be, adding that he is open-minded and optimistic. Using the same approach, he said, researchers have identified a gene for a common form of blindness.

The HapMap also has implications for the study of evolution and natural selection. Pardis C. Sabeti, a student at HMS and a postdoctoral fellow at the Broad Institute, looked for recent, common mutations in the genome. These genes are too young to have risen to their current frequency by chance alone, and so are likely candidates to be the products of recent natural selection.

Sabeti and her colleagues are currently working on a paper to reassess many previous claims about recent natural selection using the new HapMap data.

“Natural selection is always a controversial topic,” she said, “so it’s very important that we take stock carefully.”

The HapMap was born four years ago when Mark J. Daly, now an assistant professor in the Center for Human Genetic Research at Massachusetts General Hospital—one of Harvard’s teaching hospitals—and an associate member of the Broad Institute, discovered that much of human genetic variation travels in blocks, or “haplotypes,” that stay together during the genetic recombination that occurs through generations.