Scientists Map Important Gene Variation

In a major step toward one day offering gene-based customized medicine (search), scientists on Thursday unveiled the first map of common human genetic variations — patterns of DNA differences that may help forecast people's disease risks and best treatments.

This map, created by California-based Perlegen Sciences Inc. (search), is essentially the first chapter in the quest to identify tiny bits of genetic information, known as SNPs or "snips", believed key in creating gene-based medicine. A more detailed version is expected later this year.

"It is a dramatic advance," said Barbara Jasny, a senior editor at the journal Science, which published the research Thursday. The study also was presented at a meeting of the American Association for the Advancement of Science.

Public health experts view it "with a lot of excitement," agreed Lawrence Lesko, who heads the Food and Drug Administration's division of gene-based medicine.

Even unrelated people share DNA that is 99.9 percent similar. Variations in that last remaining bit are what make us individual, determining traits from our hair color to our risk of different diseases.

Until now, most genetics breakthroughs have come when a mutation in a single gene causes illness. But the most common health problems, such as heart disease, diabetes or depression, are caused by complex interactions between numerous genes and environmental or behavioral risks. Teasing out the genetic culprits under such conditions has been almost impossible.

Enter SNPs, single-nucleotide polymorphisms (search). DNA is made up of precise orders of chemicals identified with the letters A, T, C or G. SNPs are the most common type of genetic variation, sort of a spelling error — one of those letters gets out of order.

Even that tiny a difference may have profound effects.

Consider Lesko's example: Only a fraction of smokers get lung cancer, and only about 10 percent of those patients respond to lung-cancer therapy — but no one knows why, or can predict who will be the unlucky.

SNPs may hold some of those answers. The SNP map, Lesko said, gives scientists a way to study such questions and design better drug treatment.

Perlegen scientists examined the DNA of 71 Americans of European, African or Chinese ancestry, and identified 1.58 million SNPs — most of them shared across the three populations.

They're a fraction of the estimated 10 million SNPs thought to exist. But they appear to be the most common ones, said lead researcher David R. Cox.

The map does not say which SNPs cause various physical or disease-related traits.

But Perlegen, of Mountain View, Calif., is making the map available for free to other scientists to study that. Cox suggested that they compare the DNA of 400 people with high blood pressure helped by standard medicines and 400 hard-to-treat patients. A handful of SNPs may account for that variability. Once doctors know that, a simple blood test might tell them which patient should be prescribed which drug.

The goal is "to be able to use genetic information in a practical way ... while I'm still alive," Cox said, alluding to the slow progress toward gene-based medicine.

The work "is clearly exciting," said geneticist David Altshuler of the Broad Institute of Harvard and Massachusetts Institute of Technology. But he cautioned that there's no guarantee SNPs will usher in such personalized medicine, because genes aren't the only things that determine drug response.

A second version of the map, due out later this year, will contain many more SNPs. It comes from the International HapMap Project, a collaboration of government and private scientists to map patterns of genetic variation found in 270 people from Nigeria, Japan and China and Americans of European ancestry.

Researchers' goal is to be inclusive, hunting genetic variation among multiple populations because geography and ethnicity can affect people's risks for certain diseases.

But finding different SNP variations in different populations is not a biological definition of race, Cox cautioned