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'Imprinting' affects how our parents' genes work in us

Wednesday, July 26, 2000

By Michael Woods, Post-Gazette National Bureau

BAR HARBOR, Maine -- Scientists are reporting new evidence that genes people inherit from Dad don't always work like those from Mom, findings that challenge the laws of heredity set down by 19th century Austrian monk Gregor Mendel.

The findings revealed that some genes wind up with a chemical tag that proclaims "I'm from Mom," while others are footnoted "I'm from Dad."

The process, termed imprinting, silences some genes so that they don't work.

Imprinting, and the mysterious loss of imprinting that occurs in some genes after birth, have been implicated in human diseases ranging from cancer to mental illness, according to Dr. Andrew Feinberg, a medical professor at Johns Hopkins University.

"There's been enormous interest in the human genome project," said Feinberg, referring to the chemically encoded information in the 50,000 to 100,000 genes that make up humans.

"But there is a second layer of genetic information that we're just discovering. I think it will turn out to be one of the great challenges of genetics during the next five years."

Feinberg spoke at a genetics seminar in Batr Harbor.

The familiar genetics that Mendel described in his landmark 1865 laws of heredity were based on the idea that genes from each parent are equal. People inherit one paternal and one maternal copy of genes at fertilization.

Generations of geneticists, from Mendel on, thought each parent's gene had an equal function.

Feinberg and other scientists, however, have found that some genes work differently, based on the parent from whom they originate. A gene from Mom or Dad may be imprinted -- silenced, or turned off -- so that it doesn't work.

Imprinting does not affect the chemical composition of the gene. It determines whether a gene will be expressed, so that its chemical instructions are used. Scientists term this an epigenetic event, and talk of the epigenome, a set of what may be hundreds of genes whose function is determined by imprinting.

Abnormal imprinting has been linked to a number of hereditary and other diseases.

"Loss of imprinting is one of the most common features of other forms of cancer," Feinberg said, noting that it occurs in cancer of the colon, lung and prostate.

Scientists are baffled at why genes lose their maternal or paternal imprint, but suspect that exposure to environmental factors may be involved.

Feinberg cited a number of practical applications of epigenetic knowledge. Tests for loss of imprint, for instance, could be used to identify people at high risk for certain kinds of cancer. They then could get more frequent screening tests or change factors in their lifestyle that add to the risk.

In addition, researchers have exciting hints that drug therapy could be used to reverse faulty imprinting, perhaps reducing the risk of cancer or serving as a new kind of treatment.



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