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Blame Your Mother

By Magdalena Eriksson, ScienCentral News

1 August 2003: Mice with virtually identical genes can grow into quite different-looking animals—fat and yellow, or lean and brown—depending on what their mothers ate during pregnancy. As this ScienCentral News video reports, researchers are studying a twist to heredity that goes beyond our genes.

You Are What Your Mother Eats

For years, scientists have told us that our genes contain all the information about how we'll look, and even to some extent, how healthy we'll be. But Randy Jirtle, professor of radiation oncology at Duke University Medical Center , says our parents’ diets may also shape us.

Press Photo

Jirtle and his coworkers gave pregnant mice some common dietary supplements that you can buy in any health-food store: folic acid ,vitamin B12 ,betaine and choline . Then they compared the offspring of the mice that were fed the supplements with the offspring of mice that were not given supplements. Although the mouse pups looked the same when they were born, they developed in very different ways.

“When you expose the mother to those compounds, you get a variation in coat color and you shift the coat color of the offspring from primarily yellow all the way over to brown. And those brown animals now have reduced incidence of cancer, for example, diabetes, and obesity,” Jirtle says.

His mice have a gene called agouti , which makes their hair yellow. The animals in the study also have an extra little piece of DNA that has inserted itself next to the Agouti gene, where it works as a switch. A host of chemicals, including the supplements that the mice ate, can turn this type of switch either on or off. Through this recently discovered mechanism, called epigenetics , two animals can develop very differently even though their genes are identical. In this case, Jirtle calls the chemicals that act on the agouti switch "molecular stop signs".

“These stop-sign molecules find their way very readily to that switch in front of the agouti gene, and turn it off,” Jirtle says.

But different colored fur wasn't the only effect of the mothers' dietary supplements. Jirtle and his coworkers found that the yellow pups—from the mothers who did not get the supplements—ate much more than the brown pups, and ended up weighing nearly twice as much. Because they're obese, the yellow mice have a higher risk of developing cancer and diabetes as they get older.

The early embryo is most susceptible to having genes switched on or off. “That's the time in development where you need these molecules to be put on appropriate places at appropriate times. So if you don't have enough of them, or you have too many of them, you can alter what is present at a genetic level for the rest of that person's life,” Jirtle says. He also says that babies conceived through in-vitro fertilization have a higher risk of epigenetic changes. "Simply putting that fertilized egg in culture for a few days, significantly increases the incidence of developmental disorders."

Researchers believe that features which a mouse develops because of its mother's diet also can be passed on to its own offspring. So epigenetics may be responsible for quite dramatic changes from one generation to the next, which is very different from the slow evolutionary way in which our genes change over hundreds of generations.

"The epigenetic mechanisms are identical in humans. The actual genes that are affected could be different in mice and in humans, however," Jirtle says. "We really don't know what the implications are, but one point that I do want to make is that right now all our flour, for example, is fortified with folic acid. We are exposing all people to these compounds. And we don't know whether that's going to be good or bad. I think that our studies point out that we need to think a little bit more about what we are doing."

Researchers suspect that some common diseases may be caused by epigenetics. "For example, there is a feeling amongst people and parents, and also in the scientific community, that the incidence of autism is going up, and it's going up within literally one generation," Jirtle says. "This is too rapid for the underlying genetic code to be changed. It has to be through an epigenetic change, which is basically putting these little stop signs and those switches."

Jirtle believes our lack of understanding of how epigenetics works is one of the reasons why we have not found cures for behavioral diseases such as autism, schizophrenia, and bipolar disease. "I'm sure that now people will start to think of these diseases from a different light than they have in the past."

This research was published in Molecular and Cellular Biology and was funded by the National Institutes of Health (NIH) and a Dannon Institute fellowship.

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