BioWorld International Correspondent

LONDON - While the Human Genome Project documented the 99.9 percent of the genome that is common to all of us, the International HapMap Project - which published the results of its first phase in Nature last week - has charted the places in the genome at which we generally differ.

Using DNA from 269 people, the members of the International HapMap Consortium documented the architecture of common genetic variation in the population. The researchers concentrated on single base changes occurring in the genome of at least one in 100 people - the condition known as single nucleotide polymorphisms (SNPs).

The resulting map can be used to identify genes associated with diseases such as diabetes, cancer, heart disease, stroke, depression and asthma. Researchers can compare the SNP patterns of those affected by a disease with those not affected. The same test can be applied to identify variants that are likely to influence people's responses to different drugs.

Panos Deloukas, senior investigator at the division of medical genetics at the Wellcome Trust Sanger Institute in Hinxton, UK, where some of the sequencing and genotyping work for the project was carried out, told BioWorld International, "This is one more milestone on top of the sequence itself. We now have one more layer of information to place on the scaffold of the sequence, and this will allow us to pinpoint genes that are involved in disease, susceptibility to pathogens, and variable response to drugs."

He predicted that researchers would newly associate many genes with common diseases over the next two to three years and then begin determining the molecular basis for the observed phenotypes. "We are currently standing on the threshold of a real revolution in terms of identifying many new disease genes, and this in turn will increase the number of targets available for the pharmaceutical industry to tackle," Deloukas said.

One caveat, he added, was that this approach works best when the genetic variants responsible for different diseases are common. "The HapMap means we can screen people with one phenotype vs. those without the phenotype. But if the variant responsible for the phenotype is rare, it will not be possible to readily identify it," he said.

Earlier this year, even before the first draft of the HapMap was completed, a paper published in Science drew on HapMap data to pinpoint a genetic variation that increased the risk of age-related macular degeneration, which causes vision loss in the elderly.

The International HapMap Consortium comprises researchers at academic centers, nonprofit biomedical research groups and private companies in Japan, the UK, Canada, China, Nigeria and the U.S. The consortium published its phase-one results in a paper in the Oct. 26, 2005, issue of Nature in a paper titled "A haplotype map of the human genome."

In humans, there are about 10 million SNPs in which the rarer variant (polymorphism) occurs at least as frequently as 1 percent. Fortunately for researchers, SNPs that are close together on the genome tend to be inherited together. Those combinations of SNPs that have traveled together over evolutionary time are called haplotypes.

The HapMap describes chromosome regions that have sets of strongly associated SNPs, the haplotypes in those regions, and the SNPs that "tag" those haplotypes. The "tag SNPs," which can number up to 500,000, provide almost as much mapping information as the 10 million individual SNPs.

When the HapMap project started, researchers already had identified and published 2.6 million SNPs. But many chromosome regions had too few SNPs and many SNPs were too rare to be useful, so the project set out to identify more SNPs in order to form a useable map. In the course of the project, another 6 million SNPs were discovered.

The DNA samples for the study came from 269 people - 30 trios comprising two parents and an adult child from the Yoruba people in Ibadan, Nigeria; 45 unrelated individuals from Tokyo; 45 unrelated Han Chinese individuals from Beijing, and 30 trios from Utah, who were of northern and western European ancestry.

The Wellcome Trust recently announced funding of £9 million (US$15.9 million) 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, 24 human geneticists will analyze thousands of DNA samples from patients suffering from different diseases to identify common genetic variations for each condition.