Leaps in gene scan science help decode diseases

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Leaps in gene scan science help decode diseases

Progress in genetic research lets patients if they're at risk for

illness

http://www.msnbc.msn.com/id/23818970/

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. "

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 so 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. A series of genome-wide scans, the most

recent in 2005, " led to huge breakthroughs in understanding " that

disease, said 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.

Unprecedented detail

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

, 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 thousands 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.

It suggests that some genetic influence on the risk of that disease

comes from that spot or nearby. So it gives scientists a specific

place to look more closely for a disease-promoting gene.

Thinking big

In practice, genome scans can be big undertakings.

Scientists in Iowa and Denmark are searching 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 s 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

Doheny.

This scan takes about half an hour per sample. 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.

Even five years ago, such a detailed examination of DNA from so many

people would have been inconceivable.

Genome scans offer some major advantages over previous gene-hunting

techniques. Scientists don't have to start by guessing what genes

might be involved in a disease, or confine themselves to families

where a tendency to an illness is inherited.

And the genome-scan approach reveals genes with only subtle influence

on the risk of getting sick, too slight to be found by earlier

methods. That's just the kind of gene that plays a role in common

illnesses like heart disease.

Even if its impact on risk is small, a newly found gene can be a

bonanza to scientists if it reveals something new about the biology

of a disease. That in turn can give hints for finding new treatments.

Customized tests

For non-scientists, 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, " 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.

Earlier this year, for example, Swedish researchers reported

preliminary evidence that men with four or five particular gene

variants ran more than four times the risk of getting prostate cancer

than men with none of them. When family history was factored in, such

a combined test could identify men who ran a nine-fold higher risk.

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 make 10 percent of men run twice the

normal risk of prostate cancer, and 1 percent run three times the

normal risk, the company said.