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Genetic expression speaks as loudly as gene type

January 7, 2007 By Erika Check This article courtesy of Nature News.

Some ethnic differences could be down to the same genes behaving differently.

From dark skin to fiery red hair, the world's ethnic groups all have characteristic physical features. But how does our genome code for these differences? New research shows that it isn't just because different groups carry different genes some of the variation is down to the same genes being expressed differently.

The study is the latest contribution to the popular new field that uses modern genomic tools to unravel the genetic basis of variation between ethnic groups. Such analyses have only become possible recently, thanks to tools such as the International HapMap Project, published last year1, which charts the prevalence of single DNA-letter differences (called single-nucleotide polymorphisms, or SNPs) between different ethnic groups.

Such work has spotted many genetic differences between groups some of the genes that determine skin or eye colour, for example, have been unpicked. But scientists usually study one trait at a time, and only find a genetic explanation after years of painstaking work.

Richard Spielman, Vivian Cheung and their team at the University of Pennsylvania in Philadelphia, took a much faster approach, screening thousands of traits at once and working back to their genetic roots in mere months.

Express yourself

The team chose a set of 4,197 genes expressed by a single cell line. They then measured the degree to which each gene was active in this cell type in each of three ethnic groups: Caucasians, Chinese and Japanese. The Japanese and Chinese groups gave very similar results, they found. When these were lumped together and compared with the third group, the team found that 1,097 genes, or 25% of the total, were expressed very differently between Asians and Caucasians.

Spielman says the result, published in Nature Genetics2, is remarkable. "It comes as somewhat of a surprise," he says.

Spielman notes that studying other ethnic groups, genes or cell types might give different results. So this doesn't mean that, for instance, Caucasians are 25% different from Chinese people. Many other sorts of genetic variation also distinguish individuals and ethnic groups, including additions or deletions of large pieces of DNA.

But adding an understanding of differences in gene expression to the pot should help researchers to unpick why some ethnic groups tend to be more vulnerable to certain diseases than others. Cystic fibrosis disproportionately affects Caucasians, for example, and Tay-Sachs disease tends to be more prevalent among Ashkenazi Jews, French Canadians, and other groups.

"What's relevant to me is what light this might shed on medical differences," Spielman says.

Governing behaviour

The differences in gene expression may be due to differences in nearby bits of DNA: a so-called regulatory section of DNA can govern how a nearby gene behaves.

The team scanned the HapMap to find SNPs located close to the genes that were expressed distinctly in the Asian and Caucasian groups. This provides the team with candidates for specific genetic blips that might cause the variation in gene expression.

The work "adds fundamental information to our understanding of how genetic variation between individuals or populations can influence gene expression", says Steve Scherer of the Hospital for Sick Children and the University of Toronto, Canada. The research is an important step, he says, in understanding human diversity.

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  1. The International HapMap Consortium Nature, 437. 1299 - 1320 (2005).
  2. Spielman R. S., et al. Nature Genet., published online 7 January 2007. doi:10.1038/ng1955 (2007).


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