DNA scanning leads to breakthroughs

NEW YORK — 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 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.

In all, since 2005, studies with the gene-scanning technique have linked nearly 100 DNA variants to as many as 40 common diseases and traits.

"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 much just yet. Simply finding the genes that can raise the risk of an illness doesn't mean you can prevent the disease. And developing a treatment for it can take years.

But there have been some payoffs already.

One involves a leading cause of blindness in older people, age-related macular degeneration.

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 Stephen Daiger, a vision-genetics expert at the University of Texas Health Science 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 human DNA 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. But, of course, different people have slightly different DNA sequences.

And those variations are key to the genome-wide scans. Basically, scientists compare DNA from thousands of people. If sick people tend to show a result different from healthy ones, it's a red flag that gives scientists a specific place to look more closely for a disease-promoting gene.

In practice, genome scans can be big undertakings.

Scientists in Iowa and Denmark plan to search blood samples from 7,000 babies and new mothers in the United States and Denmark for genetic variations that raise the risk for premature birth.

DNA will be extracted, and early this summer, more than half a million spots on the microscopic strands from each mother and baby will be assessed for clues to where the genetic variations may lie.

The DNA will be analyzed at the Center for Inherited Disease Research at Johns Hopkins University in Baltimore. Robots will put a tiny drop of DNA-bearing solution from each person onto a clear glass slide roughly the size of a business card, with four drops per slide.

The lab's DNA scanners, blue boxes each about twice as big as a desktop printer, will reveal what DNA "letter" appears in more than 580,000 spots in the genetic material, said lab director Kimberly Doheny.

Once the results are available, the scientists will use statistical tests to find the telltale signs of a possible gene affecting risk of premature birth. They'll double-check to make sure any such signal shows up in more than one population.

Genome scans offer some major advantages over previous gene-hunting techniques. For instance, scientists don't have to start by guessing what genes might be involved in a disease, or confine themselves to families where a tendency for an illness is inherited.

For nonscientists, the most direct payoff of finding new disease genes may be in devising tests to identify people at elevated risk for a particular disorder.

Most genetic variants found in the genome scans boost a person's risk by around 50 percent. If the disease risk is fairly low, that's "not something you'd lose much sleep over," Watson said.

More useful, he said, is the notion of finding variants in maybe a half-dozen genes that affect the risk for a disease, then testing a person for all of them at once to come up with a more powerful indicator.

An Iceland-based company, deCode Genetics, announced in February that it is offering a test for eight genetic variants related to prostate cancer.

Altogether, the variants give 10 percent of men twice the normal risk of prostate cancer, and 1 percent run three times the normal risk, the company said.

There is no proven treatment to prevent the disease; the only advice to a man at higher risk would probably be for more aggressive screening for the disease.

Then there's the question about what people will do with gene-test results.

Maybe people would pay more attention to health advice if they knew they were genetically vulnerable to getting sick otherwise. But maybe not.

"I think some people will," Watson said. "I think some people just won't because they're the kind of people who aren't influenced by those sorts of things. ... I'm not pessimistic or optimistic, but I'm sure not everybody does the right thing."