Gene quest

Medical research is undergoing a sea change in its approach to linking genes to disease. Instead of hunting individual mutant genes -- a painstaking, expensive process -- researchers are more often turning to a bold, computer-driven technique that allows for fast, cheap scanning of vast regions of DNA for anomalies that can make people more susceptible to a disease or even directly trigger illness. It's not a diagnostic tool yet, but so-called "genome-wide association" research has over the past months produced dramatic results linking hitherto unexplored patches of genetic terrain with such common killers as heart disease and diabetes.

"We used to hold a single lamp" over a suspicious gene, said Dr. Francis S. Collins, director of the National Human Genome Research Institute. "Now we're able to light a whole street and survey the entire genome."

The discoveries are the fruit of two huge projects completed in this decade, the mapping of the human genome -- which showed just how similar human beings are, with each of us carrying DNA that is 99.9 percent identical -- and, just as significant , the mapping of human genetic variation, completed in 2005.

The regions of variation, although small relative to the rest of the genome, carry 10 million snippets of genetic material that vary from individual to individual.

These sections, known as single nucleotide polymorphisms, or SNPs (pronounced "snips"), cause such happy traits as green eyes or red hair. But they also are lairs for disease.

In a discovery announced last month by the Broad Institute of Harvard and MIT, researchers used SNPs technology to identify genetic variations linked to the most common form of diabetes. That was a major advance in uncovering the genetic origins of disease because the defects occurred in areas of "junk DNA" long dismissed as meaningless, according to Dr. David Altshuler, professor of medicine at Harvard and leader of the Broad research team.

The discoveries were possible only because of a powerful technique that uses thumbnail-sized "chips" smeared with DNA. Each chip can carry up to half a million SNPs, allowing researchers to scan huge swaths of an individual's DNA in seconds, at small cost. Scan results, in turn, can be quickly compared with SNP chips containing genetic material from tens of thousands of other individuals.

So, by comparing DNA from thousands of people with heart disease or diabetes, say, with DNA from healthy individuals, researchers can rapidly discover genetic variances common to those with the disease and absent from those with no illness.

COLIN NICKERSON