January 29, 2007

Insight into Ethnic Differences

A Japanese Family.

The gene varieties we inherit and the environment we've been raised in work together to shape who we are. But there’s something else involved, according to a new study: how our genes behave.

Researchers recently discovered that gene expression could naturally vary between people. Since people in certain ethnic groups tend to be vulnerable to particular diseases, a research team led by Dr. Richard S. Spielman and Dr. Vivian G. Cheung of the University of Pennsylvania School of Medicine set out, with support from NIH, to compare gene expression between populations. To do their analysis, they turned to the International HapMap Project, a worldwide effort to catalog genetic variation between people through analysis of their haplotypes—sets of DNA differences that are inherited as a group because they're clustered near each other. NIH's National Human Genome Research Institute (NHGRI) is a major supporter of the HapMap Project.

The research team examined HapMap samples from 60 Caucasian people, 41 Chinese people and 41 Japanese people. To analyze their gene expression patterns, the scientists used microarrays, devices that can measure the expression of thousands of genes at once. They chose to focus on the expression of a set of over 4,000 genes. They reported their results online on January 7, 2007, in the journal Nature Genetics.

The team found that expression levels differed between the Chinese and Japanese people in only 27 genes. However, expression levels differed between the Caucasian and Asian populations in over a thousand genes—a quarter of those tested. A subsequent analysis of 24 samples from people of Chinese descent in Los Angeles showed that they were much more similar to the Chinese and Japanese samples than the Caucasian ones.

The researchers next used the HapMap databases to look for specific genetic differences that might explain the expression differences between populations. Their analysis suggests that the key lies in regions of DNA that serve to regulate how other genes are expressed. They didn't find evidence that the regulators themselves differed. Rather, what was different was how many copies of the regulators people had.

These findings about gene expression differences may help explain why people in different ethnic groups have varying disease risks. While some population differences have been tied to variations in specific genes, genetically-determined differences in gene expression may also play a role. Further studies of variation in gene expression will shed more light on the population differences seen in complex genetic diseases.

— by Harrison Wein, Ph.D.


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