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Ethnicity tied to gene expression

SNP-driven differences in gene expression help distinguish ethnic groups

By | January 9, 2007

Ethnicity stems not just from differences in genetic sequence, but also from differences in the expression of genes shared by ethnic groups, according to a new study in Nature Genetics. The authors found that 25 percent of genes show different expression levels in Asian and European individuals, and single-nucleotide polymorphisms (SNPs) in regulatory elements likely account for many of these variations. "It's exciting to see that there is some easy explanation for expression differences between populations," said Pui-Yan Kwok, of the University of California, San Francisco, who was not involved in the study. Previous work has revealed polymorphisms that are more prevalent in some ethnic groups than in others. Some of these allele frequency differences have no known functional significance, while others are implicated in diseases such as cystic fibrosis and Tay-Sachs disease. To see if some of these polymorphisms could cause differences in gene expression levels, researchers led by Richard Spielman of the University of Pennsylvania in Philadelphia assayed gene expression differences between ethnic groups. Spielman and his colleagues measured expression levels of more than 4,000 genes in lymphoblastoid cell lines derived from individuals from three different populations: Chinese, Japanese, and European. They found that gene expression levels from the Chinese and Japanese groups were largely the same, but that expression levels between the Asian groups and the European group differed significantly for more than 1,000 genes. To pin down specific genetic differences that accounted for these differences in gene expression, the researchers compared each gene expression phenotype with 2 million SNPs known to differ among ethnic groups. They analyzed several expression profiles that were most strongly correlated with specific SNPs in both ethnic groups. The authors found that these differences in gene expression between groups could largely be explained by differences in SNPs in gene regulatory regions. The rest of the expression differences could be determined by some other factor, such as ethnic differences in which DNA sequences controls a certain gene's expression, according to the report. The authors declined to comment for this article. It's also possible that the study simply didn't detect all of the SNPs responsible for differential gene expression, noted Richard Gibbs of Baylor College of Medicine in Houston, who was not involved in the research. "You've got to be excited that they found some of these and expect that the technology won't resolve all of them, rather than think that it might be a completely different mechanism," he told The Scientist. Still, differences in predisposition to common diseases "might be linked to some of these polymorphisms governing expression," he added. The study's results are not particularly surprising, according to Aravinda Chakravarti of Johns Hopkins University in Baltimore, who was not involved in the study. "We know there is variation and that this can be used to explain expression differences" between populations, he told The Scientist in an Email. Analyzing gene expression only from cell lines may be problematic, according to Kwok. "The expression will be quite different from a living organism with environmental effects and different tissue types," he told The Scientist. "How we express these genes in our environment is what makes us healthy or sick." Melissa Lee Phillips mphillips@the-scientist.com Links within this article R. Lewis, "Race and the Clinic: Good Science?" The Scientist, February 18, 2002. http://www.the-scientist.com/article/display/12869/ R.S. Spielman et al., "Common genetic variants account for differences in gene expression among ethnic groups," Nature Genetics, published online January 7, 2007. http://www.nature.com/ng M. Torkar, "Detecting allelic variations in expression," The Scientist, August 16, 2002. http://www.the-scientist.com/article/display/20608/ J. Kling, "A SNP-by-SNP Approach Could Leave One Clueless," The Scientist, October 14, 2002. http://www.the-scientist.com/article/display/13316/ Pui-Yan Kwok http://www.ucsf.edu/dbps/faculty/pages/kwok.html L.C. Tsui et al., "Mutations and sequence variations detected in the cystic fibrosis transmembrane conductance regulator (CFTR) gene: a report from the Cystic Fibrosis Genetic Analysis Consortium," Human Mutation, 1992. http://www.the-scientist.com/pubmed/1284534 B.H. Paw et al., "Frequency of three Hex A mutant alleles among Jewish and non-Jewish carriers identified in a Tay-Sachs screening program," American Journal of Human Genetics, October 1990. http://www.the-scientist.com/pubmed/2220809 Richard Spielman http://genomics.med.upenn.edu/spielman International HapMap Consortium, "A haplotype map of the human genome," Nature, October 27, 2005. http://www.the-scientist.com/pubmed/16255080 A. Constans, "A Practical Guide to the HapMap," The Scientist, February 1, 2006. http://www.the-scientist.com/article/display/23052/ Richard Gibbs http://www.bcm.edu/cmb/?pmid=2207 Aravinda Chakravarti http://www.hopkinsmedicine.org/geneticmedicine/People/Faculty/chakravarti.html
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