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An epigenetic inheritance

It's not just genes that are inherited. Chemical tags that affect gene expression levels may be inherited too, a new study published online this week in Nature Genetics reports. Molecular biologist Arturas Petronis and his colleagues at the Center for Addiction and Mental Health in Toronto, Canada compared DNA methylation patterns from epithelial cells inside the mouths of 39 sets of identical and 40 sets of fraternal twins. Compared to fraternal twins, identical twins had more similar methyla

By | January 19, 2009

It's not just genes that are inherited. Chemical tags that affect gene expression levels may be inherited too, a new study published online this week in Nature Genetics reports. Molecular biologist Arturas Petronis and his colleagues at the Center for Addiction and Mental Health in Toronto, Canada compared DNA methylation patterns from epithelial cells inside the mouths of 39 sets of identical and 40 sets of fraternal twins. Compared to fraternal twins, identical twins had more similar methylation patterns, Petronis said, suggesting that these patterns are inherited.
The group also wanted to understand why identical twins, who share virtually all the same genes, could still wind up being so different. "One monozygotic twin could develop diabetes or cancer or arthritis, and their co-twin, the genetically identical one, could be perfectly healthy, so this is a fundamental question," Petronis said. Because twins growing up in one household generally share environmental influences, the researchers hypothesized that epigenetic differences could be a source of variability. They collected samples from three different tissues in a total of 57 sets of identical twins (including the same 39 pairs used in the comparison with fraternal twins). They then used microarray analysis to look at many different locations in the epigenome, not just an individual point mutation. "The entire epigenome is packed with differences in monozygotic twins. It's not 1 [locus] out of a 1000, it's the entire epigenome," said Petronis. While previous work looked at overall changes in the epigenome, this is the first to do a locus-specific analysis. One possible explanation for the differences in identical twins' epigenetic patterns is that small, random changes in methylation accumulate after each cell division, adding up to big differences over the life of an individual. Unlike DNA, which is very stable, epigenetic tags are more prone to change over time. So even though twins may start out with very similar epigenomes, a previous study showed they diverge over time. "The numbers and the genomic regions tested, as a proof of concept, are quite nice," said Bas Heijmans, an epigeneticist at Leiden University Medical Center in the Netherlands who was not involved in the study. "But there's much more to be done. It's really a first step." For example, the study looked at just 1 to 2% of the genome, or approximately 12,000 loci. Petronis next plans to conduct a larger study that uses a bigger sample of twins and investigates the entire genome.
**__Related stories:__***linkurl:How epigenetics affects twins;http://www.the-scientist.com/article/display/22726/
[7 July 2005]*linkurl:Gene expression is noisy;http://www.the-scientist.com/article/display/22206/
[28 May 2004]*linkurl:The Meaning of Epigenetics;http://www.the-scientist.com/article/display/12615/
[17 September 2001] __Image: flickr/nicasaurusrex__
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Comments

Avatar of: Ruth Rosin

Ruth Rosin

Posts: 117

January 19, 2009

The study is based on the premise that by comparing identical & fraternal twins, it is possible to separately determine which of their traits are due to inherited factors, and which, to the environment; or else, separately determine the percentage of the contributions of inherited factors, and of the environment, to the presence of each specific trait. \n\nThe premise is a fallacy, and, therefore, so, inevitably, are all conclusions based on it. All (!) individual traits of all (!) living organisms, develop ontogenetically, (i.e. in the individual organism), under inseparable (!) effects of both (!) inherited, and environmental factors. And inseparable means inseparable, period!!!\n\nThe study is also based on the assumption that identical twins raised in the same family, can be considered as having been raised in an identical environment, or very close to it. This assumption is also a fallacy. Although identical twins raised in the same family are often raised in similar environments, it is, in principle, impossible for them to share an identical environment, just as it is impossible for them to share the same space at the same time. (As a trivial example, just consider the theoretical possibility that one twin happens to catch a cold from someone who has a cold and is standing next to him, whereas the other twin, unable to occupy the same space at the same time, does not catch the cold.)

January 19, 2009

The process of genomic imprinting or pattern of DNA methylation occurs in the gametes - the sperm and the egg. The environment of the egg does contain cytoplasmic determinants, molecules that can affect which genes turn on and in which sequence. However, genes that are heavily methylated as in the case of the epigenome, are blocked from being transcribed. To say the environment is more influencial ignores all the experimental evidence to the contrary.
Avatar of: John Collins

John Collins

Posts: 37

January 20, 2009

In twin studies the minimum environmental effect is estimated by comparing identical twins who grew up together with identical twins who were separated early. That the methylation patterns change during life and differ more in those that were separated has long been clearly established (see for example: Vaag, Z etal (2005) Proc.Natl.Acad.Sci.USA, 102, 10604. Others show smoking leads to methylation, and thereby blockage, of genes that block cancer, apparently the opposite with green tea drinkers. This hasn't anything to do with the question addressed.\n\nIn inherited epigenetics the question is: What came through from the parents? One needs to compare children at birth with their parents. Twins might be interesting in this context but not absolutely necessary.\n\nThere have already been examples in humans which show that such an effect is more than likely, such as the small size of babies born to well-nourished individuals, who themselves were born small as a result of the war-time famine in the Netherlands. This type of adaptive plasticity would have selective advantage in evolution where the environment goes through cyclic changes (drought, cold etc.) for periods considerably shorter than a generation time of the organism. Permanent genetic changes in the genes might lead to loss of this flexibility.
Avatar of: Ruth Rosin

Ruth Rosin

Posts: 117

January 20, 2009

I never said, or even remotely suggested, that the environment is more important.\n\nWhat I stated very clearly is that it is impossible to separate the effects of inherited factors from the effects of the environment in ontogeny. Without a separation, the possibility that one would be more important, or less important than the other, does not exist.
Avatar of: Ruth Rosin

Ruth Rosin

Posts: 117

January 20, 2009

You simply refuse to understand that inseparable means inseparable; no matter what you study, and what you compare.\n\nIf you study a specific individual that was raised under a specific set of environmental conditions, (irrespective of whether he is one of a set of identical twins, or fraternal twins, raised together, or apart, or whether you compare him to his parents, or not), all you can get are the effects that his specific (!) inherited factors played in his ontogeny, inseparably (!!!) from the effects of the specific (!) set of environmental conditions under which he was raised. You get nothing more than that!\n\nDo not make the mistake of assuming that a trait that develops earlier is due more to inherited factors than to the environment.
Avatar of: Ruth Rosin

Ruth Rosin

Posts: 117

January 20, 2009

Hold it! I need to think!\n\nI have just realised that you do not question that the effects of inherited factors and the effects of the environment, are inseparable in ontogeny. What you claim is something very different. You claim that some traits that are due to inseparable effects of inherited factors and environmental factors, can have an effect on the next generation.\n\nI begin to realise that this is correct, obvious, and also trivial. Suppose a mother grew up under conditions which (inseparably from the effects of her genes), resulted in her developing serious, life-long, health problems. This could easily result in her having difficult pregnancies, with damaging birth-defects in her new-born children. So what's special, or interesting about it?
Avatar of: Ruth Rosin

Ruth Rosin

Posts: 117

January 20, 2009

Now that I have finally understood what those who speak of "epigenes" mean by "epigenes", I can imagine an almost endless number of scenarios, where traits that develop in a parent (under inseparable effects of both genes & environment), can affect the next generation.\n\nSince, in humans, parents often affect, in many different ways, what happens to their children, this is both true and trivial. Furthermore, the claim that "epigenes" are "inherited" courts trouble when you begin to consider the effects that other relatives, or friends of the family, can have on what happens with the children.
Avatar of: Donovan Haines

Donovan Haines

Posts: 4

January 21, 2009

Okay, someone explain something to me (a chemist that studies P450s, many of which are polymorphic) that I missed. The methylation patterns being more similar in identical twins doesn't sound surprising, because wouldn't the methylation be catalyzed by DNA methylases, whose genes (and their many subtle properties) would quite clearly be inherited? So the twins should have identical methylases, but non-twins may have differences/polymorphisms? Wouldn't there also be many other genes that modulate the DNA methylases that would be expected to be identical in the idential twins but potentially not in others?
Avatar of: HENRY CHANG

HENRY CHANG

Posts: 20

January 21, 2009

Before one invokes epigenetic changes, one must verify that there are no genetic changes in the tissue of interest. For example, if one monozygotic twin develops schizophrenia, it is not enough to take a blood sample and say because there are no genetic differences, it must be epigenetic. One might have to do post-mortem brain DNA sequencing to confirm mutations did not occur during development.
Avatar of: John Collins

John Collins

Posts: 37

January 22, 2009

Ruth you write: All (!) individual traits of all (!) living organisms, develop ontogenetically, (i.e. in the individual organism), under inseparable (!) effects of both (!) inherited, and environmental factors. And inseparable means inseparable, period!!! \n\nAre those baseball bats or exclamation marks supposed to intimidate the rest of us into believing that there is no way to distinguish environmental response of genes from the genes themselves? If that were true there would be no science of genetics. But there is and it is on solid ground, taking into account exactly how an organism responds to changes in its environment.
Avatar of: Ruth Rosin

Ruth Rosin

Posts: 117

January 22, 2009

I didn't say that genes cannot be separated from their effects. I said that the effects (!) of genes cannot be separated from the effects of the environments in ontogeny.\n\nMy exclamation marks are only intended to indicate that I'm sick and tired of having to repeat the same statement over & over again.\n\nYou want furtehr explanations? Check my comments in the recent discussion on SciAm online re "Evolution of the Mind".
Avatar of: Ruth Rosin

Ruth Rosin

Posts: 117

January 22, 2009

Re identical twins raised together: It is important to stress that, due to the complexity & versatility of human behavior, it is impossible for such twins to do everything together throughout their whole lives, even if they were conjoined ("Siamese") twins.\n\nIn an earlier post I imagined a scenario where one twin catches a cold from a person who is standing next to him, but the other twin, who cannot occupy the same space at the same time, does not catch the cold. I was thinking of a situation where the other twin was there. But, he could, of course, have been somewhere else altogether at that time.\n\nre "epigenes": I have tried to deal with them. But by now I realise that I do not really know what they are, i.e. I never saw a definition that would enable me to identify anything specific as an "epigene". So what exactly is an "epigene"???

January 23, 2009

The term epigenetic refers to being outside of or in addition to the genome. I do not presume to change anyone's mind regarding this topic but if I can add clarity I will gladly try. When an offspring inherits chromosomes from each parent - these carry genes which are part of the genome. Generally speaking these genes code for the production of specific proteins. If however, a gene is never transcribed and translated it is never expressed. Epigenetic inheritance involves patterns of methylation on the DNA that block this transcription thereby silencing the gene. Some genes are methylated differently in male sex cells than in female sex cells. As a result - an offspring inherits silenced genes. This "epi" inheritance is the focus of the article in question.

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