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How A Second, Secret Genetic Code Turns Genes On and Off--


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EPIGENETICS..Wow, found this article in the Wall Street Journal on Friday ...the author emailed me back with words of encouragement.

This article is truly informative. Epigenetics could possibly explain a lot about lung cancer. Make sure to read the entire article.




How a Second, Secret Genetic Code Turns Genes On and Off

By Sharon Begley

885 words

23 July 2004

The Wall Street Journal



(Copyright © 2004, Dow Jones & Company, Inc.)

WITH SOME IDENTICAL twins, a slightly different hairline or tilt of the eyebrows

reveals who's who. But for this pair of brothers, the distinguishing trait is

more obvious -- and more tragic: One has had schizophrenia since he was 22. His

identical twin is healthy.

Like all identical twins, the brothers carry the exact same sequence of three

billion chemical letters in their DNA (this is the sequence that the Human

Genome Project famously decoded). So there was no sense in looking for a genetic

difference among these usual suspects. But because schizophrenia is at least

partly heritable, scientists suspected that the twins' DNA had to differ


As I explained in last week's column, there is a second, largely secret, genetic

code beyond the well-known one of A's, T's, C's and G's that make up the human

genome sequence. Called "epigenetic," this second code acts like the volume

control on a TV remote to silence or turn up the activity of genes. It was in

these epigenetic changes that Arturas Petronis of the Centre for Addiction and

Mental Health, Toronto, and his colleagues found the difference between the


In the healthy brother, the scientists reported in 2003, molecular silencers sit

on a gene that affects dopamine, a brain chemical. In the twin with

schizophrenia, the molecular silencers were almost absent, so the gene was

operating at full volume. In another pair of identical twins, both of whom have

schizophrenia, the silencers were also missing. A pattern had emerged: missing

silencers are linked to schizophrenia, perhaps because that state of DNA

triggers a profusion of dopamine receptors. Measured by this second genetic

code, "the twin with schizophrenia was closer to these unrelated men than to his

own twin brother," says Dr. Petronis.

THIS SORT OF DNA difference would never be detected with standard genetic tests,

which scan for typos -- mutations -- in DNA sequences. But with the explosion in

epigenetics, biologists are now realizing that changes that silence and

unsilence genes, but leave the DNA sequence untouched, might explain complex

diseases better than the sequence variations that have been the holy grail for

50 years.

Take cancer. Cells harbor tumor-suppressor genes that keep them from becoming

malignant. But even when there is no mutation in tumor-suppressor genes, a cell

can become cancerous. That left scientists scratching their heads. It turns out

that tumor-suppressor genes can be abnormally silenced, by epigenetics, even

when their DNA sequence (which genetic tests for cancer detect) is perfectly

normal. So far, scientists have identified at least 60 presumably beneficial

genes that are abnormally silenced in one or another cancer, allowing tumors to

take hold.

Conversely, an unsilencing of cancer-causing genes allows these rogue genes to

turn on, Andrew Feinberg of Johns Hopkins School of Medicine, Baltimore, and

colleagues found. That triggers lung and colon cancers. "About 3% of genes seem

to be abnormally silenced or activated in cancers," says Dr. Feinberg.

Last month, a Berlin-based biotech, Epigenomics AG, reported that the

silence/unsilence pattern of one gene strongly predicts whether breast cancer is

likely to recur. Fully 90% of the women in whom this gene was operating at

normal volume were metastasis-free 10 years after treatment, compared with 65%

in whom the gene was silenced. Presumably, the gene is involved in blocking

metastasis, so silencing it spells trouble.

"Epigenetic changes are more clearly associated with the progression of tumors

than mutations are," says Dr. Feinberg. "Epigenetics may be as important in

certain conditions as the DNA sequence is in other cases."

ONE OF THE oddest discoveries in epigenetics is that genes inherited from mom

and dad are not equal. Normally, the IGF2 gene you get from dad is active, but

the copy from mom is silenced. In about 10% of people, however, the "be quiet"

tag has been lost. The unsilenced IGF2 gene is associated with colorectal

cancer, Dr. Feinberg and colleagues reported last year. Epigenomics AG is trying

to turn the discovery into a simple blood test for colorectal cancer risk.

With age, silencers on genes seem to melt away, which might help explain why

cancers and other diseases become more common the older you get. When one of the

two parental genes for a protein called homocysteine is not properly silenced,

the body produces a double dose of it; high levels are associated with heart

disease and stroke.

It is too soon to infer dietary advice from all this, but some scientists

suspect that diets too low in methyl, the molecule that usually silences genes,

may spell trouble. Sources of methyl include folate (from liver, lentils and

fortified cereals) and vitamin B-12 (in meat and fish).

Last fall, European scientists launched a "human epigenome project." It will

scan DNA for "silence" tags and link them to disease. "The human epigenome needs

to be mapped if we are ever going to thoroughly understand the causes of cancer

and other complex diseases, which we can't explain by mutations in the DNA

sequence," says Randy Jirtle of Duke University, Durham, N.C.

Let the race for this second genetic code begin.


You can e-mail me at sciencejournal@wsj.com.

Document J000000020040723e07n0000p

© 2004 Dow Jones Reuters Business Interactive LLC (trading as Factiva). All

rights reserved.

Sharon Begley

Science Columnist

The Wall Street Journal

200 Liberty Street

New York, N.Y. 10281


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Very interesting. Now if we could find someone who could figure out how to prevent them from "melting away" or encourage them to grow and protect us wouldn't that be great! Donna G

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http://www.iconocast.com/H/Health1_News ... alth9B.htm

There is a company alnylam that is developing products based on RNA interference.

Basically there are two steps to gene expression. The genetic code is in the DNA in the nuecleus. Genes are coded as base pairs of either A-T or G-C. (two different chemicals)

The two steps are:

1) Trascription

2) Translation

This code is first transcribed into messenger RNA. The message RNA leaves the nucleus and then is traslated into protiens.

By blocking the mRna (messenger RNA) the genes can be turned off. By somehow creating the mRna the genes can be turned on.

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