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Common nutrients fed to pregnant mice altered their offspring's coat color

st such a multi-generational effect. In that study of nutrition in the late 1800s, boys who reached adolescence (when sperm are reaching maturity) during years of bountiful crop yield produced a lineage of grandchildren with a significantly higher rate of diabetes. No cause-and-effect link was established, but Jirtle suspects epigenetic alterations could underlie this observation.

Humans and other animals are susceptible to epigenetic changes because of an evolutionary trait in which "junk" remnants of viral infections, called "transposons," inserted themselves randomly within the human and animal genomes. Transposons use the gene replication machinery to reproduce themselves. Cells use methylation as a means to inactivate these junk transposons and prevent their replication. Yet if the transposons have inserted themselves in or near a functional gene, the gene can be inadvertently methylated, too, thereby reducing its expression.

The scientists demonstrated that such inadvertent methylation occurred at the Agouti gene when the mice were fed the nutrients. The four nutrients encourage methylation because they possess chemicals that donate methyl groups within cells. Thus, they are primed to methylate susceptible sites in the genome. In fact, more than 40 percent of the human genome is comprised of transposons that are likely to be methylated, so any genes positioned near them could be at risk for inadvertent methylation.

"We used a model system to test the hypothesis that early nutrition can affect phenotype through methylation changes," said Jirtle. "Our data confirmed the hypothesis and demonstrated that seemingly innocuous nutrients could have unintended effects, either negative or positive, on our genetic expression."

For example, methylation that occurs near or within a tumor suppressor gene can silence its anti-cancer activity, said Jirtle. Similarly, methylation may have silenced genes other than Agouti in the present study ge
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Contact: Becky Levine
levin005@mc.duke.edu
919-684-4148
Duke University Medical Center
1-Aug-2003


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