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Gene map opens up uncharted territory

February 18, 2005 By Michael Hopkin This article courtesy of Nature News.

Patterns of genetic variation could help tailor drug therapy to particular patients

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A map has been unveiled that shows the pattern of genetic variation among people descended from populations all over the globe. The information should be a valuable resource for researchers hoping to tailor medicines to individual patients based on their genes.

To construct the map, David Cox of Perlegen Sciences in Mountain View, California, and his colleagues took DNA samples from 71 US volunteers descended from European, African and Chinese populations. They then catalogued the distribution of small genetic differences called single-nucleotide polymorphisms (SNPs).

An SNP is a single-letter change in the DNA code at a specific point in the sequence. There are millions of sites where these can occur, but little is known about their pattern and frequency.

The researchers looked at almost 1.6 million sites and laboriously recorded which of the differences were present in each of the 71 subjects. Cox presented the results at this week's meeting of the American Association for the Advancement of Science in Washington DC. They are also published in this week's Science1.

Disease markers

Many people seem to want one, but race doesn't have a DNA basis.
David Cox
Perlegen Sciences in Mountain View, California
Because they are easy to detect, researchers can use SNPs to help locate the genes involved in disease, especially conditions such as Alzheimer's and Parkinson's where individual genes make only a small contribution.

SNPs (and genes) that are close together in the genome are likely to be inherited together, so if a group of people with a particular condition shares a group of neighbouring SNPs, the odds are that a gene close by is to blame.

The snag is that it would be too time-consuming and expensive to sequence millions of SNPs for every volunteer in an epidemiological study. So Cox's project provides data that can be used to select a much smaller number of SNPs for epidemiologists to use that are representative of different inherited patterns of variation.

The map is the first of its kind. But it will soon be complemented by a second study, called the International HapMap Project, which is cataloguing around a million SNPs in 270 people. Researchers hope to publish these results later this year.

As well as being used to identify the genes involved in disease, SNPs could also help show why some people respond better than others to certain drugs. The knowledge could even lead to specific treatments tailored to a patient's individual genetic makeup.

Genetic continuum

Most of the SNPs that Cox and his team studied are common to all three populations. Around 94% were found in the African Americans, 81% occurred in the European Americans, and 74% were detected in those of Chinese ancestry. That matches the findings of previous studies in which African populations were found to be the most genetically diverse.

The researchers are at pains to stress, however, that their work is not about defining races by their genetic differences. Differences at each of the SNP sites were found within the different populations, as well as between them.

"Our paper in no way makes a scientific definition of race," Cox told the meeting. "Many people seem to want one, but race doesn't have a DNA basis. Look at human beings around the world - there are no discrete genetic boundaries; there are gradients from one end of the Earth to the other."

References

  1. Hinds D. A. et al. Science, 307. 1072 - 1079 (2005).

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