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How Acquired Diseases Become Hereditary Illnesses

One of the primary goals of genetics over the past decade has been to understand human health and disease in terms of differences in DNA from person to person. But even a relatively straightforward trait such as height has resisted attempts to reduce it to a particular combination of genes. In light of this shortcoming, some investigators see room for an increased focus on an alternative explanation for heritable traits: epigenetics, the molecular processes that control a gene’s potential to act. Evidence now suggests that epigenetics can lead to inherited forms of obesity and cancer.

The best-studied form of epigenetic regulation is methylation, the addition of clusters of atoms made of carbon and hydrogen (methyl groups) to DNA. Depending on where they are placed, methyl groups direct the cell to ignore any genes present in a stretch of DNA. During embryonic development, undifferentiated stem cells accumulate methyl groups and other epigenetic marks that funnel them into one of the three germ layers, each of which gives rise to a different set of adult tissues. In 2008 the National Institutes of Health launched the $190-million Roadmap Epigenomics Project with the goal of cataloguing the epigenetic marks in the major human cell types and tissues. The first results could come out later this year and confirm that different laboratories can get the same results from the same cells, says Arthur L. Beaudet of the Baylor College of Medicine, the project’s data hub. “One couldn’t automatically assume it would be so nice,” he says.

Up to this point, the best way to study epigenetic effects has been a strain of mice known as agouti viable yellow. In these mice, a retro­transposon—a bit of mobile DNA—has inserted itself in a gene that controls fur color. Mice bearing the identical gene can be yellow or brown depending on the number of methyl groups along the retrotransposon. Such methylation marks would normally be erased in the reproductive cells of an animal. But in 1999 a group led by geneticists at the University of Sydney in Australia discovered that methylation of the fur color genes persists in the female germ line, allowing it to be passed down to offspring like a change in the DNA.
 
 

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