Harn Posted July 26, 2004 Share Posted July 26, 2004 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. Kathy ****** SCIENCE JOURNAL How a Second, Secret Genetic Code Turns Genes On and Off By Sharon Begley 885 words 23 July 2004 The Wall Street Journal A9 English (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 somewhere. 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 twins. 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 212-416-3268 Quote Link to comment Share on other sites More sharing options...
Donna G Posted July 26, 2004 Share Posted July 26, 2004 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 Quote Link to comment Share on other sites More sharing options...
john Posted July 26, 2004 Share Posted July 26, 2004 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. Quote Link to comment Share on other sites More sharing options...
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