Human DNA Discoveries Piling Up

March 31, 2008 -- Scientists are scanning human DNA with a precision and scope once unthinkable and rapidly finding genes linked to cancer, arthritis, diabetes and other diseases.

It's a payoff from a landmark achievement completed five years ago -- the identification of all the building blocks in the human DNA. Follow-up research and leaps in DNA-scanning technology have opened the door to a flood of new reports about genetic links to disease.

On a single day in February, for example, three separate research groups reported finding several genetic variants tied to the risk of getting prostate cancer.

And over the past year or so, scientists have reported similar results for conditions ranging from heart attack to multiple sclerosis to gallstones. The list even includes restless legs syndrome, a twitching condition best known as "jimmy legs" in an episode of "Seinfeld."

Interviews with scientists at the center of this revolution and a review of published studies over the past six months make clear the rapid adoption of the new technology and the high expectations for it.

Since 2005, studies with the gene-scanning technique have linked nearly 100 DNA variants to as many as 40 common diseases and traits, scientists noted this month in the Journal of the American Medical Association.

"There have been few, if any, similar bursts of discovery in the history of medical research," two Harvard researchers declared last summer in the New England Journal of Medicine.

What does all this excitement mean for ordinary people? Not so much just yet. Simply finding the genes that can raise the risk of an illness doesn't mean you can prevent the disease.

But there have been some payoffs already.

One involves a leading cause of blindness in older people, age-related macular degeneration. A series of genome-wide scans, the most recent in 2005, "led to huge breakthroughs in understanding" that disease, said Stephen Daiger, a Houston scientist.

When scientists implicated a particular gene that's involved in a system of disease-fighting proteins in the blood, it gave scientists a "slap-on-the-forehead kind of insight...into the biology of what's going on," said Daiger, a vision genetics expert at the University of Texas Health Sciences Center.

That galvanized research into the disease. And at least one new drug is being tested in patients now.

What's made this and other hopeful findings possible is the "genome-wide association study," which lets scientists scan the entire complement of DNA from thousands of people in unprecedented detail. While the basic technique is not new, its popularity has exploded recently because of cost-cutting advances in technology and discoveries about the genome.

"It lets you go searching for that needle in the haystack," says Michael Watson, executive director of the American College of Medical Genetics.

It's a big haystack. DNA is made up of long sequences of building blocks, sort of like sentences composed from a four-letter alphabet: A, C, G and T. The human genome contains about 3 billion letters, about as many as the total number of letters and digits in more than 100 Manhattan phone books.

Scientists have identified the order of the letters in the human genome, a feat the government declared accomplished in 2003. But of course, different people have slightly different DNA sequences. People commonly differ in what letter they have at about 10 million positions along the full genome. Some folks may have a T where most people have a C, for example.

And those single-letter variations are key to the genome-wide scans. Basically, scientists compare DNA from a large number of people, some sick with a particular disease, and others healthy. They can look at a half-million or more positions to see what letter appears. If sick people tend to show a different result than healthy ones -- say, if they tend to have a T in some spot more often than healthy people do -- it's a red flag.