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A landmark science project, in which Canada played a major role, has completed the first catalogue of common genetic differences between four of the world's ethnic groups.

Some of these variations account for the difference between characteristics such as blue eyes or brown. But many of them could also mean the difference between sickness and health.

As a result, the so-called Haplotype Map unveiled in Utah yesterday, marks a historic step toward the era of customized health care -- in which treatments could be tailor made to a patient's gene type.

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The work, which has been made freely available on-line, is already speeding the discovery of genes linked to big killers like cancers and heart disease and those that predict how a person might respond to a particular drug.

"[It's]like the first transatlantic flight: once the trip was done, travel was changed forever," said McGill University's Tom Hudson, director of the Genome Quebec Innovation Centre who led Canada's Hap Map effort. "Human genetics has just crossed a similar barrier."

Using the DNA of 269 people from China, Japan, Nigeria and the U.S., the project has essentially compiled a new map of the human genome.

This one organizes the book of life encoded in human DNA into paragraphs -- known as haplotypes -- that make it exponentially easier to spot genetic mutations.

It also sheds new light on how humans evolved in different parts of the world.

For example, the Hap Map has discovered nearly four million mutations and of those, roughly 100 appear in extreme frequency in one group more than another, such as with the lactase gene type of Europeans that allows the lifetime digestion of dairy products, and the mutation that protects sub-Saharan Africans from malaria.

"This helps us to see which genes mattered to the evolution of our species," said Harvard Medical School's David Altshuler, lead author of the Hap Map report also published today in the journal Nature.

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But with this powerful new tool, tricky ethical issues could also follow. It could stigmatize people of certain ethnic backgrounds if particular disease-linked genes are more prevalent in one population. Already some ethnic groups are well known to suffer higher rates of certain diseases, the way diabetes batters aboriginal populations.

Finding genes that predispose people to disease could also lead to discrimination in health insurance or employment.

In fact, the International Hap Map Consortium struck an unprecedented team of ethicists to discuss such risks with the DNA donors, who included 90 people of the Yoruba tribe in Nigeria, 90 people in Utah of Northern and Western European descent, 45 Han Chinese in Beijing and 44 from Japan.

"We don't know what long-term associations might be made in the future [using the data]" said Bartha Knoppers, Canada Chair of Law and Medicine and co-chair of the Hap Map's ethics team. Dr. Knoppers, a University of Montreal law professor, said "past experience has shown us the risk of misinterpretation."

Scientist Charles Rotimi, from Nigeria's University of Ibadan, stressed during yesterday's press conference at the American Society of Human Genetics meeting in Salt Lake City that the Hap Map shows most genetic mutations can be seen in populations all over the world.

Dr. Rotimi also noted that his country wanted to participate so results do not "just benefit the majority populations with the monetary resources."

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In all, the three-year, $185-million Hap Map project included 200 public- and private-sector researchers in Canada, China, Japan, Nigeria, Britain and the U.S. And it grew, more than anything else, out of necessity.

Standard methods of hunting disease genes in families and remote populations had hit a wall. It worked well only for rare conditions such as Huntington's disease or cystic fibrosis that involve just one mutated gene.

But trying to find the dozens of mutated genes that increase the risk of common diseases such as diabetes, asthma or hypertension required too many patients and too much data crunching.

"Until this we were basically clueless in finding disease genes," Dr. Hudson said. "It was hit and miss, and it was mostly miss."

The concept for the Hap Map has strong Canadian roots. When geneticist Lap-Chee Tsui discovered the cystic fibrosis gene in 1989 at Toronto's Hospital for Sick Children, he noted that the mutation seemed to be found within a "haplotype," that is a block of genetic code that contains a set of mutations.

In 2001, Dr. Hudson and colleagues at the University of Toronto and the Massachusetts Institute of Technology were working on a bowel disease study with 200 Ontario families and discovered the whole genome seems to be arranged in this same block pattern -- like paragraphs in a text.

It seems parents pass down their chromosomes to children in these particular chunks. As well, genetic mutations seem to turn up in the same places in those chunks -- even in different families -- like a library where every book has a typo in the first paragraph of its third page.

In October of 2002, researchers launched the Hap Map that, like an index, would catalogue these blocks and their common mutations in diverse ethnic groups to ensure the haplotype pattern applied broadly.

This way, scientists would no longer have to scan a whole book for a typo, but simply flip to a specific page.

The result is leading to large-scale genetic studies never before possible. In Canada, Dr. Hudson and colleagues are studying 2,500 Ontario residents in the world's largest hunt for genes that increase the risk of colon cancer.

In Britain, thousands of patients are being enrolled in gene studies of eight common conditions -- including heart disease.

A U.S. group has already relied on the Hap Map, which has been uploaded to the Internet as the data came available, to find the gene mutation that increases the risk of macular degeneration, the leading cause of vision loss in the elderly.

"We should see an outpouring of discoveries in the next few years," predicted Francis Collins, director of the U.S. National Institutes of Health Genome Centre.

But in a related article in Nature, Duke University scientists warn medicine is rife with examples of gene discoveries that have not yielded new treatments or preventions.

Geneticist Steve Scherer, a senior scientist at Sick Kids, described the map as an immensely valuable research tool. But henoted, the human genome also contains common structural mutations that the Hap Map does not chart. For example, researchers now realize that some people might carry several copies of one gene instead of the usual two, or even none at all.

For this reason, Craig Venter, the scientist who mapped the private-sector version of the human genome in 2001, felt the Hap Map has a limited shelf-life because eventually researchers will not refer to generalized maps of the genome, but maps of individual people.

"It will be replaced within four or five years just by rapid genome sequencing," Dr. Venter, who runs his own research institute in Maryland, predicted in an interview this week. "The Hap Map is a very crude tool. In the short term it's a stopgap until we can have a large number of human genome sequences."

Dr. Hudson did not disagree with Dr. Venter's assessment.

But four or five years is a long time to wait, he said, for technology that might not materialize as hoped.

In the meantime, Dr. Hudson said, "We have lots to learn."

The human genome at a glance

The term human genome refers to all the DNA contained in nearly every cell of the human body.

Human DNA is the double-helix structure wound into 23 pairs of chromosomes and contains three billion chemical bits called nucleotides.

Those nucleotides are represented by the letters A,C,G and T. There are an estimated 10 million common mutations in the human genome, the places where a person might have a G instead of a T.

These single letter mutations, or Single Nucleotide Polymorphisms, are known as "SNiPs."

The Haplotype Map has so far identified 3.8 million SNiPs that tend to be inherited as a set of mutations known as a haplotype block.

SNiPs are considered common if they can be found in at least 1 per cent of the world's population.

All mutations begin as one-time copy errors during the DNA shuffle of conception. A mutation becomes more common if a carrier passes it down to many children, if it offers a survival advantage, or if a given society finds that it produces a more desirable trait.

It is felt that genetic mutations paint at least half the picture of any common disease, with the other contributor being environmental factors.

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