Geneticists hail variety show
Map of DNA differences will help experts tailor drugs.
An international team has tracked a million DNA variations in volunteers around the world, as part of an effort to map the diversity of human genes. Experts say the growing catalogue, called the HapMap, will help to pinpoint genetic causes of disease and develop more effective treatments.
"It's a major leap for genetic research," says Tom Hudson of McGill University in Montreal, who led the Canadian contribution to the HapMap.
Any two people have DNA sequences that are typically 99.9% similar. The few tiny differences between their genetic codes account for they way they vary in traits from eye colour to susceptibility to disease. Many of these differences consist of changes in single bases of the genetic code, also called single nucleotide polymorphisms or SNPs. The human genome is about 3 billion bases long, and there are roughly 10 million sites where SNPs (pronounced 'snips') are thought to occur commonly.
Researchers hope that by cataloguing SNPs and the frequency with which they occur in different populations they will boost efforts to target drugs at different genetic types. Because there are so many SNPs, the HapMap project aims to sort them in ways that will make such analyses easier.
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Earlier this year, geneticists announced that they had examined more than 1 million sites where SNPs were known to occur in the human genome, and recorded the frequency of the SNPs in 71 subjects from the United States (see ' Gene map opens up uncharted territory' ). That has now been expanded upon, with 269 volunteers contributing DNA from around the world. The database now includes Nigerians, Japanese, Chinese, and Americans with European ancestry.
When the International HapMap Consortium formed to develop the catalogue in 2002, scientists had located SNPs at 3 million sites in the genome. In the three years since then, they have discovered an additional 6 million common SNPs.
Because the process of DNA sequencing takes a significant amount of time, the team focused its efforts on 1 million SNPs spread relatively evenly throughout the genome. As well as cataloguing the frequency with which these occur in different groups of people, the team sought to find out which SNPs were linked to each other, such that where one SNP occurs a second or third is always present.
It turns out that the presence of each of the million SNPs can be detected by testing SNPs from a subset of around 500,000. That will help researchers to do more efficient genetic studies, says Mark Daly, a computational biologist with the Broad Institute in Cambridge, Massachusetts, and member of the HapMap consortium.
The team has also gathered data about 3.5 million extra SNPs from its pool of international volunteers, and has posted these on its website. The next step is to crunch through these data to map out the SNPs and see how they relate to each other.
Hudson notes that researchers have already begun using the data to shed light on the genetic causes of certain disorders. He and his colleagues will use HapMap to guide their colon-cancer research.
And HapMap shows how differences between ethnic groups can be very subtle. For example, across the 1 million sites examined, only 11 always contained a different genetic base in the Nigerian samples when compared with the same site in the European samples.
"This speaks to the fact that the genetic differences between different populations in various geographic areas are minor," says Daly.
But although the absolute differences between the various ethnic backgrounds are tiny, there are genetic trends that differ between ethnic groups. A given set of SNPs may be linked in one way in Asian populations for example, but in a different way in Europeans. Over the whole genome there are more differences between individuals than there are between ethnic groups, but such trends are still thought to be useful for targeting drugs.
Hudson stresses that not all people within an ethnic group share the same SNP pattern, so pharmaceutical companies should bear this in mind. "We would want to give a drug not based on the colour of someone's skin but based on the presence or absence of the genetic markers," he says.
- International HapMap Consortium, Nature, 437. 1299 - 1320 (2005).
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