tag:blogger.com,1999:blog-6146376483374589779.post3362567816869880071..comments2024-02-14T11:18:50.296-08:00Comments on Wiring the Brain: The Trouble with Epigenetics (Part 2)Kevin Mitchellhttp://www.blogger.com/profile/07172255754953214162noreply@blogger.comBlogger37125tag:blogger.com,1999:blog-6146376483374589779.post-16241112197536832562013-12-28T23:32:29.371-08:002013-12-28T23:32:29.371-08:00duvetica Jackets
Bottom line is, I didn't retu...<a href="http://www.duveticashop.eu" rel="nofollow">duvetica Jackets</a><br />Bottom line is, I didn't return to Apple to make a fortune. I've been very lucky in my life and already have one. When I was 25, my net worth was $100 million or so. I decided then that I wasn't going to let it ruin my life. There's no way you could ever spend it all, and I don't view wealth as something that validates my intelligence.<br />ERAM jeehttps://www.blogger.com/profile/05838732995970298539noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-79129441975354110162013-12-22T07:09:44.658-08:002013-12-22T07:09:44.658-08:00Your time is limited, so don't waste it living...Your time is limited, so don't waste it living someone else's life. Don't be trapped by dogma - which is living with the results of other people's thinking. Don't let the noise of others' opinions drown out your own inner voice. And most important, have the courage to follow your heart and intuition.<br /><a href="http://www.parajumpers.org.uk/pjs-outlet-shop" rel="nofollow">parajumpers shop</a><br />Gujjarhttps://www.blogger.com/profile/14016645823515164786noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-25682833186701662582013-12-20T09:28:25.861-08:002013-12-20T09:28:25.861-08:00The most important single ingredient in the formul...The most important single ingredient in the formula of success is knowing how to get along with people. <br /><a href="http://www.researchproposalwriting.biz/" rel="nofollow">write my research proposal</a><br />Gujjarhttps://www.blogger.com/profile/14016645823515164786noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-87279777771258305872013-12-04T04:17:52.703-08:002013-12-04T04:17:52.703-08:00Take up one idea. Make that one idea your life - t...Take up one idea. Make that one idea your life - think of it, dream of it, live on that idea. Let the brain, muscles, nerves, every part of your body, be full of that idea, and just leave every other idea alone. This is the way to success.<br /><a href="http://www.zhosho.com" rel="nofollow">Moose Knuckles</a><br />Gujjarhttps://www.blogger.com/profile/14016645823515164786noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-31585725086188643112013-10-31T09:23:33.341-07:002013-10-31T09:23:33.341-07:00very useful blog i like it this is the most useful...very useful blog i like it this is the most useful way to provide help to others<br /><a href="http://www.personalstatementlawschool.net/" rel="nofollow">law school personal statement</a>reward.ff.garena.comhttps://www.blogger.com/profile/08063262627719293099noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-56134552553187346752013-10-28T23:07:27.081-07:002013-10-28T23:07:27.081-07:00It's not a good example of epigenetic monetary...It's not a good example of epigenetic monetary gift via the gametes, and that is what may be recommended as being a quite possibly critical device. <a href="http://essays.me.uk/" rel="nofollow">cheapest essay writing service review</a>pratishthahttps://www.blogger.com/profile/08247674828363134254noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-47603568116420922532013-10-03T15:20:13.515-07:002013-10-03T15:20:13.515-07:00"The possibility that interacting with a stre..."The possibility that interacting with a stressed or strung-out male animal will alter the behaviour of the female, post-mating, so that maternal care is also changed."<br /><br />>> In the following model, tests revealed that maternal behavior was normal: http://www.ncbi.nlm.nih.gov/pubmed/?term=20673872<br />Besides, in vitro fertilization has been associated with changes in epigenetic markers: http://www.ncbi.nlm.nih.gov/pubmed/23714435Anonymoushttps://www.blogger.com/profile/15026526343185815913noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-22582580670841024612013-09-26T16:43:37.400-07:002013-09-26T16:43:37.400-07:00Tesla and Elon Musk
http://www.youtube.com/watch?v...Tesla and Elon Musk<br />http://www.youtube.com/watch?v=SrzMdoKPPaA<br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-31512681979643221782013-06-14T08:37:24.638-07:002013-06-14T08:37:24.638-07:00Proper education for Sustainable Development is mu...Proper education for Sustainable Development is must . It should include key sustainable development issues into teaching and learning. <br /><a href="http://computerscience.thesiswritingservice.com/statisticsmathematics-service/" rel="nofollow">statistics help</a>reward.ff.garena.comhttps://www.blogger.com/profile/08063262627719293099noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-11615457945539910092013-06-06T12:31:08.538-07:002013-06-06T12:31:08.538-07:00I build $82h whereas i am traveling the planet. La...I build $82h whereas i am traveling the planet. Last week I worked by my laptop computer in Rome, Monti Carlo and at last Paris…This week i am back within the USA. All I do square measure simple tasks from this one cool web site.go to this site home tab for more detail .... JOBS34.COMAnonymoushttps://www.blogger.com/profile/10493238933219460041noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-6134099350019419882013-05-09T05:19:17.190-07:002013-05-09T05:19:17.190-07:00I am new to the blogging stuff so I do not have an...I am new to the blogging stuff so I do not have any idea to express my thoughts over here. Please share more information on your post.<br /><br /><a href="http://americanbobbleheads.com/specialbobbleheads-c-54.html" rel="nofollow">Best American Specialbobbleheads</a>Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-9176336040278493292013-04-23T11:40:42.797-07:002013-04-23T11:40:42.797-07:00As individuals, people are inherently good. I have...As individuals, people are inherently good. I have a somewhat more pessimistic view of people in groups. And I remain extremely concerned when I see what's happening in our country, which is in many ways the luckiest place in the world. We don't seem to be excited about making our country a better place for our kids. <br /><a href="http://www.linkedincourses.net/" rel="nofollow">linkedin training courses</a><br />Gujjarhttps://www.blogger.com/profile/14016645823515164786noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-82081758785787521732013-04-18T06:23:29.670-07:002013-04-18T06:23:29.670-07:00Thanks for those comments. Here are a couple recen...Thanks for those comments. Here are a couple recent relevant articles that make similar points: http://www.ncbi.nlm.nih.gov/pubmed/19416939 and http://www.ncbi.nlm.nih.gov/pubmed/23584020Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-57576955771995631282013-04-18T03:14:07.318-07:002013-04-18T03:14:07.318-07:00I agree very much with your points. The problem, w...I agree very much with your points. The problem, when one wants to cite something to support a bit more caution with throwing that explanation around when genetic explanations exist and are better validated, is that, there are few journal articles to cite for this position (perhaps it's usually vented in a blog or on Twitter), but so many that make very all-encompassing conclusions from little data (e.g. Jablonka & Raz, 2009) or scientists who don't really care about the pathway for their result and just throw in a small "or it could be epigenetics" somewhere to please the crowd.<br />Can you recommend any neutral articles that emphasise how implausible it is that aberrant epigenetic variation plays a large role in complex traits? I mean other than textbooks that emphasise the whole "rebooting" thing (I mean this is a thing that people not very familiar with genetics may just not know, but it seems condescending to cite a textbook).Unknownhttps://www.blogger.com/profile/13130751541232572015noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-41791007605880407922013-02-03T00:47:21.897-08:002013-02-03T00:47:21.897-08:00Let's see, I am no expert, but...in my 64 year...Let's see, I am no expert, but...in my 64 years I have seen such a change in "values" from one generation to the next and the next(and I have been alive for 3 generations...), you would have to convince me that conditions such as autism (a term which is an invention of the late 20th century I believe), was not around when I was a youngster. <br /><br />I dont know why this "label" exists. Do we label visibly disabled people as "cripples" or worse? Please do not "label" kids!! <br /><br />Its funny how on skimming briefly through the posts here, I picked up on the fact that it was a crime of uneducated parents who swallowed potions way back when, to ease symptoms of pregnancy, that were probably to blame for certain modern anti-social behaviour from small children. (I acknowledge the thalidomide tragedy as the travesty that it was, and that this has been scientifically proven to have been a direct result of the drug) - but how about those modern parents feeding drugs to their toddlers and young children, which they are able to supposedly justify (to their own great relief) because their child's unacceptable behaviour has a name now, ADHD or Autism?? I will bet you anything that good old-fashioned discipline has NEVER been dished out to any of these children when they were toddlers? Were long explanations and sophisticated "reasoning" more the order of the day? I will bet they were! <br /><br />Some parents think there isnt a happy medium between a sharp smack on the backside to a 3yr old for rotten behaviour, and the other extreme of broken bones and bruises! Give me a break!<br /><br />Spare the rod and spoil the child.. we have come a long way from those Victorian principles thank God, but yes, there IS a happy medium, and we need to get back to the parental DUTY of reasonable disciplining of small children. This is how we show children we love them when we balance this discipline with affection and nurturing for the great majority of the time. We hope that by our efforts, we will release them into a world where they will be loved and lovable, respectful and respectable, aspiring to better themselves, humble and yet confident, and more. We want this for them. <br /> <br />Children are not stupid..they constantly "test", its how they learn their boundaries... they DO know when their parent has any reservations about dishing out the discipline they ought to get- on the spot! A recipe for on-going behavioural problems from kids for sure is to show any self-doubt or inconsistency in management of their kids' bad behaviour. Way too many of the youngest generation have way too many negative behaviours which we adults are not handling well in my opinion and which seem to be getting more prevalent over time from my own observations. <br /><br />Kids need leadership and love. And yes, discipline is most definitely a part of that. You will not convince me otherwise, having raised our kids and seeing the values we used as our guidelines to raising well-balanced, loveable individuals pay off, as our grandchildren are a modern reflection of our success at being parents to their parents. <br /><br />Claims to the contrary have no substance, we will always find excuses in the name of scientific statistics. But this new-age idea of treating young children as small adults is a recipe for trouble. We do already have enough evidence in the up-and-coming teenage generation to back this up. There is a very sinister element out there which is becoming more and more obvious and I believe is a direct indictment of parental permissiveness on an out-of-control scale.<br /><br />There are certainly heritable behavioural conditions I definitely believe, such as schizophrenia, panic disorders, depression and more which do need addressing, often on an ongoing long-term basis, but I am plainly not talking about those.Nanny Dearesthttps://www.blogger.com/profile/16483209287140692372noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-47643571287839002372013-01-31T19:06:48.464-08:002013-01-31T19:06:48.464-08:00Another evidence against this model of epigenetic ...Another evidence against this model of epigenetic inheritance is that increased paternal age is a risk factor of autism but increased maternal age is not.Guyhttps://www.blogger.com/profile/17242527831298435835noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-71844099956598211912013-01-27T23:52:25.699-08:002013-01-27T23:52:25.699-08:00Thanks Matt. The scenario you suggest should indee...Thanks Matt. The scenario you suggest should indeed increase heritability (de novo mutations have the same effect). That is not generally what has been proposed in the field, however - that epigenetic markers of some experience affect some germ cells and not others. Still, it's clearly testable, as you say.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-60951437089995831222013-01-27T23:50:52.454-08:002013-01-27T23:50:52.454-08:00See here for very relevant article by Montgomery S...See here for very relevant article by Montgomery Slatkin on: Epigenetic inheritance and the missing heritability problem http://www.ncbi.nlm.nih.gov/pubmed?term=slatkin%20m%2C%20epigenetic<br /><br />This reinforces the point that epigenetic inheritance, even if it is a general phenomenon, can not contribute to heritability.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-6316531738487914752013-01-27T09:45:28.899-08:002013-01-27T09:45:28.899-08:00"unless the supposed epigenetic marks affect ..."unless the supposed epigenetic marks affect MZ twins more consistently than DZ twins (and there’s no reason why they should)"<br /><br />If the epigenetic mark occurs heterogeneously in the female germline--some eggs have it, some don't--it would cause MZ twins to be affected more consistently than DZ twins. I don't know if this actually occurs, but it's a testable hypothesis.Matthttps://www.blogger.com/profile/01356184969078882294noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-3165472755235363852013-01-22T14:28:42.057-08:002013-01-22T14:28:42.057-08:00I should read the paper you linked to in your orig...I should read the paper you linked to in your original post, but I thought there were reproducible SNPs among autistic populations. A similar challenge exists in late-onset alzheimer's, where the strongest associated signal is APOE e4. This variant isn't enough to cause AD and the etiology varies a lot between populations.<br />There is a genic CpG island in exon 4 of this gene, the exon with the mutations. APOE exon4 also has a strong transcriptional element within this hypermethylated region, an enhancer that is differentially modified according to the different alleles and with cell type specificity. It alters promoter activity of APOE locus genes, APOE, TOMM40 and APOC1. Knowing that AD effects behavior and this hypermethylated CpG affects expression of the most well-known gene associated with AD how would you go about testing whether, as you say, epigenetics are a source for variation as opposed to a mechanism by which other causes can have their effects. I don't actually see much of a distinction between the two. <br /><br />Environmental effects on disease etiology are often very difficult to show even for seemingly obvious candidates. Take obesity for instance. Some scientists say the obesity epidemic is due to the overproduction of food. But that can't be the whole story. What's making people want to "over eat"? Pernicious advertising, poverty, genetics, etc? <br /><br />I'm not invoking environmental factors as the main cause of autism. Is this an argument in the scientific community? I will point out that increased recognition and diagnosis can be influenced by technology and industry (e.g., ADHD and Ritalin).<br /><br />caynazzohttps://www.blogger.com/profile/11263280738905977688noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-4098564593957194442013-01-22T07:50:07.587-08:002013-01-22T07:50:07.587-08:00I would indeed be interested in any literature tha...I would indeed be interested in any literature that shows convincing evidence for a gene-by-environment effect in autism etiology (or even a straight-up environmental effect for that matter). But please note that that is not what these posts were about. They were about (i) whether epigenetics can be considered a *source* of variance for behavioural traits and psychiatric disorders (I say no), as opposed to a mechanism by which other causes can have their effects (I'm perfectly happy with that). And (ii) whether there is good evidence for transgenerational epigenetic inheritance for these kinds of traits (i.e., transmission of acquired behaviours by epigenetic marks in gametes) - again, I say no. And there is no need for that hypothesis because these disorders are demonstrably highly heritable and those kinds of mechanisms can't contribute to that. <br /><br />I do not doubt that some environmental factors can cause epigenetic changes as well as genetic changes, which could, in theory, contribute to risk of some disorders in those exposed. That is a separate topic and one I will happily accept can occur, given some good evidence (that they happen at all, and that they contribute to overall risk). If environmental factors are being invoked to explain the supposed "autism epidemic", I think it is pretty clear now that that rise is due mainly to increased recognition and diagnosis.<br /><br />Finally, you may think these are semantic distinctions, but that was the whole point of these posts - that it is important to define these terms so people don't get confused between the multiple possible meanings. Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-81200143254665519732013-01-22T06:59:36.507-08:002013-01-22T06:59:36.507-08:00Oy vey, Kevin, my head is spinning at your comment...Oy vey, Kevin, my head is spinning at your comment that "there is not currently any good evidence for (epigenetic mechanisms) or any need for that hypothesis." Your position is scientifically illiterate and reactionary in the extreme.<br /><br />The autism/neurodevelopment literature over the past five or so years has positively exploded with evidence for such g x e etiology. Would you like me to supply a complete list of references? <br /><br />Thanks to Guy and Caynazzo for their wise observations.Prenatal Hormone Exposurehttps://www.blogger.com/profile/03368476982711975099noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-44894210098815168252013-01-22T00:34:53.157-08:002013-01-22T00:34:53.157-08:00As much as I think GWAS are looking in the wrong p...As much as I think GWAS are looking in the wrong place (at common variants only), they are now very well controlled and very rigorous, statistically (especially in controlling for false positives). But I reiterate the fact that just because these kinds of studies have not found genetic variants that can explain the observed heritability of various disorders does not mean that these disorders are not in fact caused by differences in DNA sequence. So, until we have properly surveyed rare mutations (which are much more likely to have a phenotypic effect), there is no need to jump ship and start invoking epigenetic mechanisms. Especially when there is no good evidence of their involvement in these disorders and they cannot explain heritability as determined from twin studies. I am not dismissing the possibility that epigenetic mechanisms are involved in some way in the etiology or pathogenesis of these conditions - I am just saying there is not currently any good evidence for it or any need for that hypothesis. Given that is the case, skepticism seems the appropriate position.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-90452824016759661772013-01-22T00:20:23.157-08:002013-01-22T00:20:23.157-08:00I absolutely 100% agree that non-additive interact...I absolutely 100% agree that non-additive interactions are likely to be very important. I just think the important ones are more likely to be between rare mutations than common variants. And as we have not looked for rare variants properly (by sequencing lots of people) that is what I think we should do now, while also developing better ways to look for the non-linear effects of combinations of mutations.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-87431874948366311062013-01-21T12:05:50.254-08:002013-01-21T12:05:50.254-08:00I get the impulse to go expansive, to do something...I get the impulse to go expansive, to do something more than write a blog post journal clubbing a few papers and instead make a point about "the state of things." But your take home message--epigenetics isn't the answer--is incoherent. You obviously like hypothesis driven studies over exploratory research, yet in the context of this post, you forget to mention that GWAS, also exploratory and which you correctly defend, is highly susceptible to p-value fishing and high false negative rates. Maybe you just don't like/get epigenetics. Can you point to any sound epigenetic papers out there or are they all just like that xkcd cartoon? <br /><br />And then there's this.<br />"Jut because we haven’t found them yet doesn’t mean we should start looking somewhere else." <br /><br />That's special pleading. For instance, why not? I only see this statement as meaningful if you qualified it by showing that looking elsewhere has been proven to drain precious resources from a sure thing. Notably you haven't laid out what that is other than exclaiming "GENETICS" at us. More better GWA studies? Maybe. There will be no single answer to missing heritability in complex neurological disorders. A good place to look will be phenotypic variation within populations due to hidden environmental structures within those populations effecting genes (GxE). The proper time to consider dismissing epigenetic contributions to complex neurological disorders is when the equivalent GWAS have been done and have shown to produce no reproducible effects. Those studies just aren't there on any comparable scale. <br /><br />If you haven't read it already: "Transgenerational genetic effects on phenotypic variation and disease risk" Human Molecular Genetics, 2009.<br /><br />"GWASs currently focus on DNA sequence polymorphisms or on DNA copy number variation. But if offspring phenotype can be impacted through epigenetic inheritance, then it should be possible to survey methylation and histone marks as well as parentally-derived RNAs and proteins to test for the molecular changes that account for traits and diseases in offspring.caynazzohttps://www.blogger.com/profile/11263280738905977688noreply@blogger.com