HMS Center Helps Draft Genome ‘HapMap’

The Harvard-affiliated Whitehead Center for Genome Research has started work with 14 other research groups worldwide to map variant genes thought to underlie common diseases like diabetes, asthma and cancer.

The research groups recently received a $100 million grant from the International Human Genome Project to jumpstart the work. For its part, the Whitehead Genome Center has been given $8.4 million to help construct a catalog of DNA variations, called the “International HapMap.”

The HapMap will not aim to identify the genes related to specific diseases, but instead to create a useful tool for this kind of research.

David M. Altshuler, assistant professor of genetics at Harvard Medical School, is the principal investigator on the Whitehead Center’s project.

He has worked to identify genes associated with disease and found that a genetic variant common in the human population increases the risk of contracting type 2 diabetes.

“If we know that there are five different variations of a gene, then we can determine the frequency of each variation in people with diabetes or heart disease,” he explained.

The idea for the HapMap comes from work done at the Whitehead Center, where researchers found that human DNA has been inherited generation after generation in large, unchanged blocks and has not yet changed significantly.

These large blocks of DNA are known as haplotypes and the HapMap will chart their location throughout the human genome.

Researchers developing the map will study the genomes of people in four different ethnic groups—Chinese, Japanese, the Yoruba people of Nigeria and Americans of Northern and Western European descent.

According to Altshuler, some population geneticists question just how much genetic variation the map will be able to capture.

But “the variation of the human popualtion genome is so simple and structured that the Hapmap will be surprisingly complete—showing 80-90 percent of the variation,” he said. “This is basically a given.”

He said the project’s potential usefulness in determining the relation of genes to disease is less clear, however.

“How often will this 80-90 percent be the stuff that causes the disease is the question we still have to answer,” Altshuler said.

Indeed, some researchers have major reservations about the project for this very reason—questioning whether the HapMap approach can be useful in tracking down the variant genes involved in common diseases.

Kenneth M. Weiss, a population geneticist at Pennsylvania State University, said it will be difficult to determine the appropriate number of genetic markers necessary for the HapMap project’s objectives.

But more broadly, he said, he does not believe that mapping of the human genome is a useful way to approach study of disease.

The Whitehead Center’s research comes after the $3 billion human genome project successfully sequenced a single human genome—but did not catalog the variations thought to underlie common diseases.

Altshuler said he is excited to be in the middle of this burgeoning field of research.

“Its like working on the moon-shoot in the sixties,” he said, “I feel very lucky to be living in this time and doing this work.”