• 08 October 2005
• From New Scientist Print Edition.
• Bob Holmes

Knowing where our great-great-great-grandparents and beyond came from is more than a genealogical curiosity. It is giving geneticists a powerful tool for understanding the genetic basis of diseases such as multiple sclerosis, schizophrenia, diabetes and prostate cancer.

These and other diseases have been difficult nuts to crack because they are caused not by a single genetic flaw but have multiple genetic and environmental causes. This makes the links between gene and disease subtle and hard to find. In fact, it has been virtually impossible until now.

David Reich, a geneticist at Harvard Medical School, and his colleagues have now found a better way to search for genes that increase the risk of multiple sclerosis (MS). They have done so using a technique called admixture mapping, which relies on the fact that many African-Americans have a mixture of African and European ancestry that dates back only the few generations since their ancestors' arrival in North America.

As MS is more prevalent in people of European ancestry than those of African origin, Reich reasoned that African-Americans with the disease should be more likely to carry European versions of any genes that contribute to MS. To investigate, his team took genetic samples from 605 African-Americans with MS and 1043 without it. The researchers scanned each person's genome for 1082 genetic markers that have differing frequencies in people of African and European origin.

On average, each person inherited 21 per cent of their genome from European ancestors, the researchers found. But when they looked more closely, they found the people with MS were significantly more likely to possess European genes on a region of their genome near the middle of chromosome 1. That means there might be an MS-related gene there, even though that region, which contains 68 known genes, has never been linked to MS before (Nature Genetics, DOI: 10.1038/ng1646). "We have no idea which gene it is," says Reich, who is now conducting further tests to narrow down the search.

“Geneticists have found a powerful tool for understanding the genetic basis of diseases such as MS and diabetes”

The admixture-mapping technique does have its blind spots, Reich notes. For example, his analysis failed to pick up another region, on chromosome 6, that is already known to affect MS risk, because the gene frequencies in people of European and African ancestry do not differ in this region.

But the technique should be capable of detecting genes linked with other diseases, such as hypertension and prostate cancer, whose prevalence differs in people of African and European descent. Reich also suspects it might work for some diseases that affect both groups equally, because the two lineages could have different risk genes that add up to a similar disease risk. Moreover, similar analyses could apply to Hispanic Americans, who are also a recent admixture of European, African and Native American ancestries.

From issue 2520 of New Scientist magazine, 08 October 2005, page 18

http://www.newscientist.com/channel/health/mg18825204.100;jsessionid=EMDENEFJNADG