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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.'"
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From TFA:
...
Sometimes imprinting goes awry before birth, leaving a normally silenced gene "on" or silencing one that should not be.
Now a question is how imprinting may be changed to reactivate an imprinted gene after birth.
Am I the only one concerned by this statement?
I believe that understanding epigenetics will have a huge impact on human medicine. If we learn how to turn different genes on and off we could do all sorts of amazing things. It's already clear that a number of health problems are related to having a gene in the wrong state.
you're missing the point entirely. This isn't just a few cells that are affected, this is your entire population of cells. if you inherit a gene from your father that is "switched off" and that gene is the only one that can be inherited [only from Y chromosome for example] then you're kind of screwed. There isn't a second copy that is switched on and functional to prevent the associated disease caused by the first gene being switched off. There are a lot of these kind of genes that are regulated in the levels of expression and on/off states of the gene. Hardly mundane.
Sigs are too short to say anything truly profound so read the above post instead.
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.
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.
Stay sentient. Don't drink bad milk.
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.
Sigs are too short to say anything truly profound so read the above post instead.
Were they silenced for political reasons? or what?
What?
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.
Seven puppies were harmed during the making of this post.
On the Duke news site they give more information about how they came to their findings. They mention that they fed data about the sequences of genes known to be imprinted, and likely to be non-imprinted genes into a computer to check for differences. Based on that, they searched for other sequences that resembled the imprinted ones. That's why the results are just good guesses and more research need to be done to determine if they are true positives.
Knowing that one of the copies is imprinted helps in three ways -
(a) It helps provide people with genetic counseling e.g. helps in deciding if you want to continue with a pregnancy if you know that your fetus has a genetic defect on the paternal copy (and the maternal copy is silenced) by sequencing an amniocentesis sample.
(b) More fundamental to this is that, is that this might help pin down a gene defect as the cause of a disease. For example you might find some locus often associated with a disease but in the patients you sequence the genes, it turns out one of them has got a perfect copy and the other has a mutation. Since it is difficult to say for a majority of mutations if they would affect function or are simple polymorphisms in the population, you continue searching other genes. OTOH, if you know one of the copies is shut down, and you see one copy has a mutation, you promptly analyze this candidate gene a lot more.
(c) Finally, of course for proper cure, it helps to know what the defect is. e.g. if you know it is a defect in an ion transporter, you might try some types of drugs and if it is an inflammatory defect you will try something else - so (b) is useful in guessing plus making animal models to test them.
(d) there is the hope that one day we will be able to fix things gene therapy which again is dependent on figuring out the molecular defect by (b).
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)?
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Stay sentient. Don't drink bad milk.
Sigs are too short to say anything truly profound so read the above post instead.
It's not a mutation! You inherit two copies. One of these copies is disabled EPIGENETICALLY. It's not mutated, it's methylated. This is a reversible process. The choice of which of these two copies is methylated is very important, because some tissues/cells work with the paternal and others with the maternal copy. This is why some times you get diseases with variable penetrance (autosomal dominant, but not always present or present in variable degrees, for example).
Concerning the treatment, if you can reverse or control epigenetic silencing, you can alter a persons genetic profile by choosing which copy (paternal or maternal) is active. This is currently impossible.