Some genes get shushed along the way

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Some genes get shushed along the way

Scientists find in a twist in how people inherit genes from mom and

dad

http://www.msnbc.msn.com/id/22030616/

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 now 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 Friday by the journal Genome

Research.

Next comes work to prove exactly what role these genes play. " Some

will be real gold and some will be fool's gold, " Jirtle added.

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.

When genes go awry

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.

She said finding which genes are imprinted is important for a bigger

question: How do behavioral or environmental factors tip the balance

for someone who is genetically predisposed to a health problem?

Environmental influences

Previous work by Jirtle and others shows the environment can

reprogram how some genes operate, making them speed up or slow down

or work at the wrong time. In a groundbreaking 2003 experiment,

Jirtle fed pregnant mice different nutrients to alter the coat color

of their babies. The feed affected chemical signals that control how

hard a certain gene worked, determining when the babies had yellow

coats like mom or brown ones.

" It's not just about the sequence of your genes, but how that

sequence is turned on and off by environmental exposures that is

likely to determine whether you will be healthy, " Volkow said.

Imprinted genes " are likely to be particularly susceptible to

environmental factors. "

Sometimes imprinting goes awry before birth, leaving a normally

silenced gene " on " or silencing one that should not be. Faulty gene

imprinting leads to some devastating developmental disorders, such

as Angelman syndrome, which causes mental retardation.

Now a question is how imprinting may be changed to reactivate an

imprinted gene after birth.