Gene map paves the way to personalised health care

By Maggie Fox in Washington
February 19, 2005

The first published map of human genetic differences has been released, with scientists declaring it will offer a significant step towards truly personalised medicine, from predicting who will get what disease to finding ways of choosing the best drug for an individual patient.

The map, published on Thursday, looks at more than 1.5 million tiny genetic differences among 71 people, said the team who created it at Perlegen Sciences, a spin-off of the California-based gene chip maker Affymetrix.

Perlegen's chief scientific officer, David Cox, said the map was enough to find some of the most common genetic variations involved in disease.

"This project sets a new milestone in the search for genetic elements linked to complex genetic diseases such as Alzheimer's, cancer and multiple sclerosis," he said.

The idea was not to find one or two "disease genes" but instead to look for patterns that can account for how a person may respond to specific high blood pressure drugs, for instance, Mr Cox and colleagues reported in yesterday's issue of the journal Science.

"It's kind of like being a matchmaker," Mr Cox told a news conference at the annual meeting of the American Association for the Advancement of Science. Eventually, he hoped, individual doctors would be able to consult such a map to determine what drug to prescribe to a patient.

This would build on existing policy at the US Food and Drug Administration, said the agency's Lawrence Lesko, an expert in pharmacogenomics - the field of using genetic patterns to predict drug reactions.

Already, targeted cancer drugs are approved for a narrow group of patients, such as breast cancer patients eligible to use Herceptin, he said. "You are excluding using the drug in a non-responder," Mr Lesko told reporters.

A map like Perlegen's might provide the first step towards screening out those in a population likely to have a toxic response to a drug, he said.

One example is the COX-2 inhibitors, analgesics being reviewed this week by Food and Drug Administration experts because they raise the risk of heart attacks, strokes and heart disease in some patients.

To make the map, Perlegen, working with researchers from US universities, scanned 71 Americans of African, European and Asian descent, picking out 1.58 million of the most common single-letter variations in the genetic code, called single-nucleotide polymorphisms.

The genetic map is made up of combinations of nucleotides known as A, C, T and G. Different combinations of these spell out the amino acids that in turn make up genes and other important genetic areas.

The current maps of the human genome, published in 2001, use combinations of human genes, all combined together to make a picture of the "average" human map.

But to understand why one person has high blood pressure, or why another cannot tolerate aspirin, the differences must be teased out.

The new map is a very small start, Mr Cox said.

But David Altshuler of Harvard University and the Massachusetts Institute of Technology warned that not all drug reactions and disease outcomes would boil down to genetics. Environment is sure to play a role, he said.

"The predictive value [of genes] may not be high," he said.