Archive for Friday, November 30, 2007

Scientists map which genes are switched on, off

November 30, 2007

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Normally, children inherit one copy of a gene from mom and a second from dad.  But children sometimes inherit a "silenced" copy of a gene, one programmed to be switched off.  If something harms the remaining good gene, there's no backup.

Normally, children inherit one copy of a gene from mom and a second from dad. But children sometimes inherit a "silenced" copy of a gene, one programmed to be switched off. If something harms the remaining good gene, there's no backup.

— Remember biology class where you learned that children inherit one copy of a gene from mom and a second from dad? There's a twist: Some of those genes arrive switched off, so there is no backup if the other copy goes bad, making you more vulnerable to disorders from obesity to cancer.

Duke University scientists have identified these "silenced genes," creating the first map of this unique group of about 200 genes believed to play a profound role in people's health.

More intriguing, the work marks an important step in studying how our environment - food, stress, pollution - interacts with genes to help determine why some people get sick and others do not.

"What we have is a bag of gold nuggets," lead researcher Dr. Randy Jirtle said about the collection of "imprinted" genes. The team's findings were published online today by the journal Genome Research.

Usually, people inherit a copy of each gene from each parent and both copies are active, programmed to do their jobs whenever needed. If one copy of a gene becomes mutated and quits working properly, often the other copy can compensate.

Genetic imprinting knocks out that backup. It means that for some genes, people inherit an active copy only from the mother or only from the father. Molecular signals tell, or "imprint," the copy from the other parent to be silent.

Jirtle compared it to flying a two-engine airplane with one engine cut off. If the other engine quits, the plane crashes. In genetic terms, if one tumor-suppressing gene is silenced and the active one breaks down, a person is more susceptible to cancer.

Only animals that have live births have imprinted genes. It was not until 1991 that it was proved that humans had them. Until now, only about 40 human imprinted genes had been identified.

The Duke map verified those 40 and identified 156 more. Researchers fed DNA sequences into a computer program that decoded patterns pointing to the presence of imprinted genes instead of active ones.

Many of the newly found imprinted genes are in regions of chromosomes already linked to the development of obesity, diabetes, cancer and some other major diseases, the researchers reported. One, for example, appears to prevent bladder cancer. A second appears to play a role in causing various cancers and may affect epilepsy and bipolar disorder.

Scientists had thought imprinted genes would account for about 1 percent of the human genome. While scientists must double-check that the newly identified ones are truly silenced, the new map matches that tally.

"It's a fascinating paper," said Dr. Nora Volkow, director of the National Institute on Drug Abuse. Volkow praised the new mapping method for speeding the slow discovery of these genes.

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