July 23, 2004

Genome affects disease in new ways

Read more... Schizophrenia Biology

Human genome cracked? Not quite.

Scientists in Europe recently launched the "human epigenome project." Epigenome refers to a "hidden" genetic code, not the one that contains information for building protein molecules, but the one that determines when those genes are turned on or off. The epigenetic code is now being implicated as a probable cause for numerous disease, schizophrenia among them.

For example, in a recent twin study, one brother is healthy while the other is diagnosed with schizophrenia. Because they are identical twins, they should have exactly the same genetic code. Well, almost. The surface genomes - the one detectable with standard genetic tests that scan for mutations - were identical. However, the healthy brother had numerous "molecular silencers," molecules that block the genes responsible for making the neurotransmitter dopamine. The brother with schizophrenia had almost none; thus, his dopamine genes were producing much higher levels of neurotransmitter than his brother's.

"Silencer" molecules, that control when a gene is turned on or off, are the products of the epigenome.

Measured by his epigenome, not his genome, the schizophrenic brother appeared more closely related to other schizophrenia patients than to his own twin brother. They also were missing the dopamine silencers.

Epigenetic changes may be behind other diseases as well. For example, the body normally contains tumor-supressing genes that prevent rogue cancer cell growth. However, some patients develop tumors even when these genes contain no mutation. In these cases, it looks like the genes are being silenced at inappropriate times by epigenetic changes. A reverse situation can also happen; sometimes genes can be abnormally turned on by epigenetics, causing uncontrollable cell growth and the appearance of a tumor.

"Epigenetic changes are more clearly associated with the progression of tumors than mutations are," says Dr. Andrew Feinberg, a researcher at Johns Hopkins School of Medicine. "Epigenetics may be as important in certain conditions as the DNA sequence is in other cases."

It also appears that gene silencers normally present in the body begin to disappear with age, providing a possible explanation for why older people are more likely to develop chronic diseases.

To read the full news article, see "How a Second, Secret Genetic Code Turns Genes On and Off" (July 23, 2004) in the Wall Street Journal, p. A9.

To read more about epigenetics and Dr. Feinberg's research at Johns Hopkins, see "The Mystery of Epigenetics" in the Winter 2004 edition of Hopkins Medicine online magazine (http://www.hopkinsmedicine.org/hmn/W04/medrounds.cfm#9)


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