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Duke Scientists Map 'Silenced Genes'

Zonk posted more than 6 years ago | from the you-in-the-back-speak-up dept.

Biotech 42

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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fuck Piquepaille (1)

Adolf Hitroll (562418) | more than 6 years ago | (#21547461)

I am sure he's happy now !

Name (0)

Tablizer (95088) | more than 6 years ago | (#21547527)

I suggest they call this area of DNA the "Mafia section".

Re:Name (1)

asCii88 (1017788) | more than 6 years ago | (#21549959)

I would, if only I understood what are they talking about.

slashdot summary is terrible..... (5, Informative)

tloh (451585) | more than 6 years ago | (#21547531)

From the article, a bit more pertinent background:

Usually, people inherit a copy of each gene from each parent and both copies are active, programmed to do their jobs whenever needed. If one copy of a gene becomes mutated and quits working properly, often the other copy can compensate.

Genetic imprinting knocks out that backup. It means that for some genes, people inherit an active copy only from the mother or only from the father. Molecular signals tell, or "imprint," the copy from the other parent to be silent.

With (0)

Dunbal (464142) | more than 6 years ago | (#21547593)

The exception of cancer and the oncogenes, and the second exception of this happening at an extremely early stage (around gastrulation time), I don't get it. What does my pancreas care if a single Beta (insulin producing) cell dies/mutates, or a single bone marrow cell dies/mutates, etc? I don't think this research will have as "profound" effects on human health as they would like us to believe. Although no doubt it's yet another link in the chain that will finally lead us to understanding intra-nuclear biochemistry.

Re:With (3, Informative)

Anonymous Coward | more than 6 years ago | (#21547707)

I believe that understanding epigenetics [wikipedia.org] 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.

Re:With (3, Insightful)

wizardforce (1005805) | more than 6 years ago | (#21547717)

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.

Re:With (1, Interesting)

Dunbal (464142) | more than 6 years ago | (#21548379)

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.

Re:With (4, Insightful)

LooTze (988596) | more than 6 years ago | (#21548677)

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).

RNAi, Small Molecule Treatment (1)

sanman2 (928866) | more than 6 years ago | (#21549417)

Scientists are searching for small molecules that can have epigenetic effects of switching genes off or on. So these new epigenetic maps of active and silenced genes can help guide research on which genes to target for small molecule therapy. Also, RNA interference (RNAi) is another method for genetic activation/deactiviation, and as that technique improves, it may be possible to use it for therapeutic medicine in humans.

Re:With (1)

vorpal22 (114901) | more than 6 years ago | (#21549727)

While perhaps you might also be able to identify non-desirable traits that are more likely to be passed on to offspring

This, IMO, could be incredibly valuable alone. For example, I have Crohn's Disease, and knowing that it's very likely that there's a genetic component to my condition, I would never even consider having biological children; even if the chance that they'd inherit it from me is fairly small, IMO, given the effects of this disease, it's completely irresponsible for me to consider having a child of my own.

If my parents could have known that there was a significant chance that a child of theirs would develop Crohn's Disease and with this knowledge, they instead opted to go the route of adoption, their existence and my lack thereof would have placed all parties in a much better situation.

Of course, that's not to say that they wouldn't have taken the risk all the same. I know several people with Crohn's Disease that do decide to have children (some of which have developed Crohn's themselves), but I find it very difficult to muster up any respect for these parents.

Re:With (1)

bvimo (780026) | more than 6 years ago | (#21555717)

Fifteen years ago I found out that I had inherited Ankylosing Spondylitis from my father. I saw the pain that he suffered from and I know that I will one day also have similar problems. I took the decision that I wouldn't have any children, it hasn't been easy. I've lost several potential wives in recent years, which I greatly regret. I heard a programme on the BBC Radio 4, one afternnon on the way home from work. It's a weekly 30 minute science show, this week three scientist were bubbling with enthusiasm over an RNA fix for DNA problems. It sounded like science fiction. I've not heard anything about it since.

Re:With (2, Insightful)

wizardforce (1005805) | more than 6 years ago | (#21550167)

Completely irrelevant. Unless you are in a position to DO something about it.
just a note, the university I am doing my studies was one of the first to work in this area so yes I could probably end up doing something about this.

We already know there are many lethal gene combinations, that produce in utero abortion or neonatal death. Your point is?
just a note that not all changes in gene expression cause in utero abortions.

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.
even better a whole mechanism for many genes being altered- anything that methylates cytosine residues will alter gene expression although they also increase the incidence of point mutations because of hyrolysis of 5'cytosine to thymine.

However as far as I know, altering the gene in a single cell will damage THAT cell
sigh... you over simplify this far too much. You never considered the fact that these kind of changes in expression become very important in egg and sperm cells which combine to produce the next generation passing on the change in expression that occured in one single cell. if the same thing happens in the zygote you can see that that single change in expression for that particular cell can have great consequences.

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.
gene expression can be altered possibly alleviating illness, not only that but eugenics is out of the question.

Is this how you plan to "fight" disease? I am not sure I want to live in that world.
the only one that implied such a future is *you* for I certainly do not want to see such a future.

Re:With (2, Insightful)

Anonymous Coward | more than 6 years ago | (#21551339)

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?

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.

mod parent up (0)

Anonymous Coward | more than 6 years ago | (#21553683)

best explanation of epigenic process as it occurs in gene imprinting in this entire thread.

Re:With (3, Interesting)

tloh (451585) | more than 6 years ago | (#21547797)

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.

Re:With (4, Interesting)

wizardforce (1005805) | more than 6 years ago | (#21547911)

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.

Re:With (2, Interesting)

SacredNaCl (545593) | more than 6 years ago | (#21548897)

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)?

Re:With (2, Interesting)

Dunbal (464142) | more than 6 years ago | (#21548305)

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.

Re:With (2, Informative)

tloh (451585) | more than 6 years ago | (#21549705)

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.
If this leads to advancement in the treatment of cancer (even if only cancer), I think many would consider it to be a holy grail enough. But then, to the credit of the article's author, no where in the article did they allude to this research result being a Panacea for all of humanity's ills. I may not have a biology degree (yet) but I don't have to in order to understand the article. However, I'm a bit confused by your comprehension of the article. You seem to be under the impression that an imprinted gene leads to a single affected cell being damaged/killed and that is of no consequence. That's not what the article is talking about at all. Genomic imprinting happens during the formation of gametes which means the entire organism which develops is affected. What is relevant to the article is that the *consequences* of genomic imprinting for an organism which has no insurance policy to handle the environmental influences on it's development. If environmental factors *are* of consequence, you can bet that the effect is not going to be felt by just a single cell or affect just a single gene. In other worlds, if, for example, you diet is to be considered a risk factor, every cell (all containing the same allele of the imprinted genome) in you entire body is going to be subjected to what you eat. But since most diseases are not caused or controlled by a single gene, we can only speak of raised or lowered risk due to the nature of exposure. The article specifically mention that "imprinted genes are in regions of chromosomes already *linked* to the development of obesity, diabetes, cancer and some other major diseases". They never said such are the definitive causes of such diseases.

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?
Are we talking about the same stem cells? If a damaged progenitor cell gives rise to mature lineage cells of the circulatory system, it seems certain that the odds of those decedents all having the same gene damage are 100%. If environmental exposure can cause one cell to acquire genetic damage, the odds are that is not an isolated occurrence and you will end up with defective cells from far more than just one mutated stem cell. Health hazards would not called that if they affect only one or two cells would they?

....and becomes less functional, but this has nothing to do with malfunctioning genes.
In another post, you made mention of being "able to identify non-desirable traits that are more likely to be passed on to offspring" and "inherited a non-functional gene for the GLUT-2 glucose transporter". If this is your notion of gene imprinting, you don't really understand the process at all. Imprinting is an epigentic process (as someone else has already mentioned). It is a non-sequential manipulation of gene expression that doesn't alter the gene itself. The affected gene is turned on/off through methylation but is otherwise completely intact and functional. In fact, in each generation, the old imprints are "erased" in the gamete-producing cells and the chromosomes of developing gametes are newly imprinted according to the sex of the individual. For a given species, the imprinting pattern always follow a consistent maternal/paternal line generation after generation. But nowhere does the process of imprinting destroy or damage the gene itself.

University Scientist (0)

Anonymous Coward | more than 6 years ago | (#21547595)

If I was a university scientist, my motto would be "What we have is a bag of gold nuggets, bitches", then I'd be all like, "We've created the first map of this unique group of about 200 genes believed to play a profound role in people's health.", then under my breath I'd be like, "bitches."

Uh (2, Insightful)

goldaryn (834427) | more than 6 years ago | (#21547605)

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?

Un-Used Knowledge is Useless (1)

Smordnys s'regrepsA (1160895) | more than 6 years ago | (#21547811)

Why concerned, but not ecstatic?

If you had no plan on applying genetic research, there would be no worldly reason to perform the research in the first place. Sure, Science for Science's sake is fun, but I'm sure a 1000x1000 grid Sudoku puzzle that used every known symbol would be just as consuming/fulfilling. More to the point, if you want further high-level research you need financial backing (Investors usually invest in projects that have a chance of a positive return).

Re:Uh (1)

Renraku (518261) | more than 6 years ago | (#21548357)

Nope, not at all.

It might be the first step to a good measure of control over certain genes.

Or more deadly bioweapons.

Re:Uh (1)

vuffi_raa (1089583) | more than 6 years ago | (#21552773)

or gene replacement therapy, which means that you could become a clone of anyone's genes that you could get your hands on..... as well as reactivating the genes with HGH therapy and shooting yourself through a 2nd growth stage that would make you younger..... c'mon what 90 year old man wouldn't like to be an 18 year old paris hilton

Nobility of spirit (0)

hyades1 (1149581) | more than 6 years ago | (#21547615)

I shall heroically resist the overwheliming temptation to link the terms "silenced genes" and "beanless chili" in a sentence.

I deserve and expect applause.

At last! (1)

nih (411096) | more than 6 years ago | (#21547655)

with a story like that dnf will rock when it ships!

DNA job application (1)

ragedriven (1047722) | more than 6 years ago | (#21547667)

we are that much closer to a future like in "Gattica"

Re:DNA job application (0)

Anonymous Coward | more than 6 years ago | (#21548343)

When did the "I" base was discovered?

Re:DNA job application (1)

Garridan (597129) | more than 6 years ago | (#21549373)

Grammer what you did mess up?

Re:DNA job application (0)

Anonymous Coward | more than 6 years ago | (#21550077)

,Obviously. The acid synthetic nucleic program research in

Duke Scientists Map 'Silenced Genes' (0)

FrostedWheat (172733) | more than 6 years ago | (#21547771)

Hail to the gene, Baby!

DNA methylation controls imprinting (3, Interesting)

Anonymous Coward | more than 6 years ago | (#21547783)

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.

Now there is real tech in Firehose (0)

Anonymous Coward | more than 6 years ago | (#21547855)

I know, this is a bit off topic.

But we need to hear about people who eat too much and now blame their genes for eating too much? Me, I am quite happy admitting every flaw I have is mine! Yep, MINE! No excuses.

Now are /. readers becoming nerd want-a-bees and want to see foo-foo stuff or are we really into nerd stuff like how OpenDS/Sun people got sacked?

Probably give us an option to disable firehose, it seems hosed.

Yes but (3, Funny)

iminplaya (723125) | more than 6 years ago | (#21547975)

Were they silenced for political reasons? or what?

Abandonware (1)

russlar (1122455) | more than 6 years ago | (#21548273)

So God wrote abandonware, too? Cool! Makes me feel better about developing for OS9.

machine learning (5, Informative)

Takichi (1053302) | more than 6 years ago | (#21548333)

On the Duke news site [duke.edu] 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.

Oversimplifiction alert! (1)

clayski (214528) | more than 6 years ago | (#21553473)

Like most articles on Science in the popular press, this article is oversimplified to the point of not being true anymore.

Epigenetics is a relatively new field that deals with several new layers of the language of DNA that are only recently beginning to be understood. The 2007 Nobel Prize in Physiology or Medicine went to Fire and Mello for their work in uncovering a phenomenon known as RNA interference that is a key part of epigenetic inheritance.

Imprinting happens during gamete formation. It is a process of modulating the level of expression of one or both of the 2 copies of a gene in a diploid organism, and it can apply to cells in a specific tissue type or globally throughout the organism. Imprinting in some cases can be reversed if the remaining copy of a gene is damaged, in other cases it is irreversable. Sometimes the organism reads only the copy of a gene inherited from the male parent and sometimes only from the female parent, sometimes bothe are expressed but the LEVEL of expression differs between the 2 copies.

(For the genetically literate, genes are imprinted by converting euchromatin to heterochromation, and/or by moving genes to silencing compartments within the nucleus during cell differentiation where transcription does not take place).

Imprinting is one reason why cloned organisms have genetic problems. During normal gamete formation, imprinting is removed and genes are re-imprinted in a different manner. Scientists are working on understanding how this is done and what the rules are, in order to produce adult-origin stem cells and for cancer treatment, among other things.

The bottom line is we are at the stage of knowing that it exists, and a reasonable amount about the mechanism, but we don't grok the language of imprinting yet. If you actually want to learn about the current understanding of this topic, you have to go to the scientific literature because very few textbooks even mention it yet, and those that do are using a outdated understanding of the concept. Anything published before 2005 on this topic is likely to contain information that we now know isn't true.

NOVA did a special on Epigenetics (http://www.pbs.org/wgbh/nova/genes/) (PBS.ORG) that was only slightly oversimplified.

Lamarck (1)

jbengt (874751) | more than 6 years ago | (#21553823)

From TFA: "Previous work by Jirtle and others shows the environment can reprogram how some genes operate, making them speed up or slow down or work at the wrong time. In a groundbreaking 2003 experiment, Jirtle fed pregnant mice different nutrients to alter the coat color of their babies. The feed affected chemical signals that control how hard a certain gene worked, determining when the babies had yellow coats like mom or brown ones."

So were Lamarck's dismissed theories partly right?

Re:Lamarck (1)

GastonTheTruck (1048316) | more than 6 years ago | (#21558881)

No - Lamarck fabricated most of his results. Different levels of gene expressions have been known about since the start of genetics itself, usually they are accounted for via statistics (gene expression as a probability rather than a certainty). The environmental effects on genetics are very different from Lamarckian concepts. It's more unexpressed potential, rather than a primarily environmental driven process the Russians thought they had uncovered.
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