Duke Scientists Map 'Silenced Genes'

palegray.net writes "Wired reports on new research into the phenomenon of 'silenced genes', genetic constructs that have no 'partner' in case one goes wrong over the course of your lifetime. Scientists at Duke University have mapped some 200 genes that may 'play a profound role' in the health of the average human. '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 ... 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.'"

DNA methylation controls imprinting

[Anonymous Coward]

Not all genes are expressed by both the maternal and paternal lines. Some genetic defects are caused because both copies express themselves when one should be turned off. I'm sure the controls and implications will turn out to be more complicated than we know. But this is just another area where all the heat is epigenetic.

Presumably this natural imprinting occurs when the DNA gets reprogrammed during fertilization. The de-methylation and re-methylation determines which sequences get turned off. The attempts at cloning using somatic nuclear tranfers skip this crucial step and are found to have different methylation patterns than natural cells. This leads to defective imprinting that may be the cause of the anomolies found in Dolly and others and may be the cause of the abnormally large offspring of clones as they are over-expressing some genes and have others turned off that should be on.

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[tloh]

IANAB, but perhaps you're overlooking environmental factors that influence gene expression and are potentially damaging to normal cellular functions. Also, cancers and oncogenes would be the rule rather than the exception as it is notorious for doing the exact kind of thing this research is aiming to treat. Think if you will, of a smoker who's been dumping craploads of toxins and mutagens onto his/her lung tissue for years at a time. It won't be just one or two cells that mutate or die. Also, if the gene that fails happens to be in one or two of those bone marrow cells that are responsible for churning out blood cells and/or maintaining your immune system, you're risk of developing leukemia increases dramatically. Because since cancer is essentially uncontrolled cell growth, it will quickly overwhelm any normal body functions if not stopped.

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[wizardforce]

you are correct, the gist of the research goes like this:
1) some genes can be switched on or off by environmental factors [chemicals, other genes etc.]
2)if one of these cells that has a switched on/off gene just happens to be a sperm cell or an egg, it can carry that epigenetics to the next generation.
3) some genes can only be inherited functional from one parent
4) if that parent happens to be the one that has the inactivated [switched off] gene then that gene is entirely non-functional in the offspring because there is no functional back up gene from the other parent.
this leads to the conclusion that environmental factors can alter gene expression which can be inherited to offspring which under some conditions and genes no longer have a functional gene that may or may not prevent disease, that is to say if the gene is inactivated you're likely to get the associated disease. In many cases, these genes are thought to be involved in obesity, heart disease, cancer etc. which means that environmental factors in your parent's lives or even your grandparent's may contribute to you being more likely to get a certain disease associated with a non-functional gene.

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[Dunbal]

As you said, you are not a biologist. Leukemia is a type of cancer, and I specifically excluded cancer in my post. This research may be relevant to cancer (ONLY, in my opinion). However it's not the Holy Grail it is presented as.

There are many stem cells in the bone marrow and wiping one of those cells out will not lead to aplasia. And we're talking about millions of cells getting the exact same gene damaged - in theory. Now what are the odds of THAT?

As for your other example, we are well aware of the pathological/biochemical mechanisms behind chronic inflammation and the changes it can produce in the lung or other tissues. Cells die, tissue structure is altered - most of the time by the host's own immune response - and becomes less functional, but this has nothing to do with malfunctioning genes.

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[Dunbal]

Hardly mundane.

      Completely irrelevant. Unless you are in a position to DO something about it. We already know there are many lethal gene combinations, that produce in utero abortion or neonatal death. Your point is?

      Now if you could point out a case of a single gene being altered AFTER embryogenesis (by environmental factors or whatever) that produces disease, then we're talking about eventually being able to work on a way of preventing this. However as far as I know, altering the gene in a single cell will damage THAT cell only. Now with the exception of the cancers (which I made in my previous post) please point out a disease resulting from a mutation of a single cell?

      While perhaps you might also be able to identify non-desirable traits that are more likely to be passed on to offspring, this won't be much use until you start obliging probable carriers to be sterilized.

      "Sorry Mr. Smith we've spotted that you have inherited a non-functional gene for the GLUT-2 glucose transporter and therefore since you only have one working gene your children are at risk for type II diabetes, please report for sterilization?" Is this how you plan to "fight" disease? I am not sure I want to live in that world.

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[SacredNaCl]

I wonder how much two way transfer there is between bacteria, viruses and human genes. We know the bacteria are far from static targets, and some of them definitely have the ability to influence your genes (in particular ones that hijack cells like cell wall deficient bacteria) and vice versa. We see far higher rates of certain "autoimmune" diseases in health care workers, likely for this reason. But it might point out another factor in why they get sick and another health care worker exposed to the same organisms doesn't. I'm also wondering if some of these infectious organisms might acquire the ability to turn off copies and if this factor is not a static target over a lifetime (in which case genetic risk counseling might be pretty wildly inaccurate depending on later exposures)?