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Heart gene yields insights into evolution, disease risk

y, Rockman and their colleagues explored the evolutionary history of one particular variant in a gene called MMP3. Such variants are called "alleles."

The MMP3 gene is one of a family of genes that serves as the blueprint for a protein enzyme with a broad array of functions in the body. However, the variant they studied does not affect the structure of the protein itself, but regulates how much of the protein is produced in the cell. The variation, or polymorphism, is tiny, adding one genetic unit, or nucleotide, to the more than 1,600 that make up the regulatory region of the gene.

However, the single alteration in the MMP3 protein regulatory region causes a functional difference that has important clinical implications. The MMP3 protein is an enzyme that plays a role in regulating the elasticity and thickness of blood vessels. While its effects are complex, said the researchers, overall the variant they studied tends to retard the progress of coronary artery heart disease

Because of this clinical effect, considerable human data had been gathered on the MMP3 variant, said Rockman, making the gene attractive in exploring the possible effect of natural selection on the frequency of the variant. Also, he said, the nature of the variation offered an opportunity to study how mutation, selection and the demography of populations contribute to the variation in the gene and its effects on disease.

"People have long been studying the evolutionary role of variation in genes that affect the structure of the proteins for which they code," he said. "However, a huge fraction of the genome consists of segments that don't code for a protein, but are regulatory regions for the gene. This is really an under-explored region of the genome, and we we're hoping to find out more about how it evolves and what role it plays in complex traits."

Rockman, Wray and their colleagues first compared the structure of the gene region among non-human primates
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Contact: Dennis Meredith
dennis.meredith@duke.edu
919-681-8054
Duke University
6-Sep-2004


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