tag:blogger.com,1999:blog-6146376483374589779.post167450564524197501..comments2024-02-14T11:18:50.296-08:00Comments on Wiring the Brain: The genetics of emergent phenotypes Kevin Mitchellhttp://www.blogger.com/profile/07172255754953214162noreply@blogger.comBlogger21125tag:blogger.com,1999:blog-6146376483374589779.post-36727926905905241752015-11-12T08:59:17.540-08:002015-11-12T08:59:17.540-08:00Great article! I found that a very useful way to t...Great article! I found that a very useful way to think about genotype/phenotype relations. Excuse my ignorance with regard to genetics, but with regard to chorionicity studies into schizophrenia (Davis et al. 1995 "Prenatal development of monozygotic twins and concordance for schizophrenia"), would that imply that some insult during gestation affects the gene expression of both twins similarly? Do the genes need to change, or can this be explained by cell death or other higher-level effects?Anonymoushttps://www.blogger.com/profile/10773800661244829824noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-90182640650996293092014-07-02T00:56:01.903-07:002014-07-02T00:56:01.903-07:00Very interesting to read this article.I would like...Very interesting to read this article.I would like to thank you for the efforts you had made for writing this awesome article.<a href="http://www.plumlivinghealth.org" rel="nofollow">plumlivinghealth</a> | <br><br /><a href="http://www.provitalhealth.org" rel="nofollow">provitalhealth</a> | <br><br /><a href="http://www.northernhealthplan.org" rel="nofollow">northernhealthplan</a> | <br><br /><a href="http://www.oralhealthexam.org" rel="nofollow">oralhealthexam</a> | <br><br /><a href="http://www.cwyzehealth.org" rel="nofollow">cwyzehealth</a> | <br><br /><a href="http://www.cwyzehealthcare.org" rel="nofollow">cwyzehealthcare</a> | <br><br /><a href="http://www.healthykskids.org" rel="nofollow">healthykskids</a> | <br><br /><a href="http://www.biohealthchip.org" rel="nofollow">biohealthchip</a> | <br><br /><a href="http://www.meridianwomenhealth.org" rel="nofollow">meridianwomenhealth</a> | <br><br /><a href="http://www.heroeshealthproject.org" rel="nofollow">heroeshealthproject</a> | <br><br />Anonymoushttps://www.blogger.com/profile/10108809794771915520noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-90789267377127709892014-06-18T04:13:07.989-07:002014-06-18T04:13:07.989-07:00This comment has been removed by the author.Clarity Adepthttps://www.blogger.com/profile/01942708690978579702noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-15959961207996989882014-06-03T05:38:10.362-07:002014-06-03T05:38:10.362-07:00I would definitely buy that book! Love these posts...I would definitely buy that book! Love these posts - they provide plenty of food for thought.Dean D'Souzahttps://www.blogger.com/profile/17074749060825213986noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-85700212888659693642013-10-07T20:49:37.717-07:002013-10-07T20:49:37.717-07:00Hi.. I'm very much interested in Science.. Esp...Hi.. I'm very much interested in Science.. Especially in your domain... Thanks a lot for your great sharing.. Try this site to know about salon..<br /><a href="http://www.SarahJanine.com" rel="nofollow">hair salon chattanooga</a>Anonymoushttps://www.blogger.com/profile/01066636916242968072noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-21515781972641226682013-05-13T23:25:52.614-07:002013-05-13T23:25:52.614-07:00I've recently started a blog, the info you off...I've recently started a blog, the info you offer on this web site has helped me greatly. Thanks for all of your time & work.<br /><br /><br /><a href="http://caregiverinsandiego.com/" rel="nofollow">Caregiver San Diego</a>Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-59448647073632034872013-05-09T03:28:42.474-07:002013-05-09T03:28:42.474-07:00I am new to the blogging stuffs so i do not have a...I am new to the blogging stuffs 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://abutterflyrelease.com/" rel="nofollow">glass clinic</a>Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-42964746565165318302013-04-05T00:32:14.373-07:002013-04-05T00:32:14.373-07:00Thanks Dwight for your kind comments and also for ...Thanks Dwight for your kind comments and also for a great question. It is an issue I have struggled to try and make sense of too - if the program of neural development is so robust then why can it be disrupted by single mutations in so many different genes? One possible answer is that the genetic network controlling development has evolved robustness to deal with environmental variance and, more importantly, intrinsic noise in the system. It can deal with small fluctuations of many components because it has evolved to do so. As a byproduct, it evolves robustness to mutations- at least to the cumulative effect of many minor mutations (like SNPs). There may be less selective pressure to evolve robustness to major mutations because that requires a kind of foresight that evolution does not have - the system does not know it might be advantageous in the future to evolve more robustness now to a challenge it has not yet encountered. When it does encounter it - when a mutation arises in a specific individual - it is too late. I realise that's all a bit hand-wavy, but trying to answer "why" questions in biology always is! <br /><br />Another possible factor is that maybe the system is not so hypersensitive to mutations - maybe we're just really good at detecting what are actually minor changes in the function of the system because we are so attuned to interpreting each other's behaviour: http://www.wiringthebrain.com/2012/08/are-human-brains-especially-fragile.html Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-15162395553898334322013-04-04T11:39:40.714-07:002013-04-04T11:39:40.714-07:00Thanks for this thoughtful piece and your many oth...Thanks for this thoughtful piece and your many other excellent contributions to the scientific literature. They are a pleasure to read. I am a cognition and 'schizophrenia' researcher, with a strong interest in genetics, and I have been struggling with many issues that you touch on here and elsewhere. I find your characterization here of schizophrenia, epilepsy, etc, as 'specific failure modes' very persuasive. Other pieces I have read, including some of your articles, make a strong case for the importance of highly penetrant, rare genetic variants as a starting point for such complex disorders. I am having trouble drawing these two threads of thinking together, though. It seems that, if 'typical' brain wiring is based on a probabilistic yet very robust program, it should require more than a single nudge to redirect the program into a pathological but stable alternative. I understand that you are not arguing for Mendelian-like transmission in every case, but I guess I feel instinctively that there should generally be a more complex constellation of causal factors undelying a developmental endpoint as complex as psychosis. Thanks. Dwight Dickinsonhttps://www.blogger.com/profile/04859350935463265585noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-20512290389029455402013-03-26T08:35:42.109-07:002013-03-26T08:35:42.109-07:00Todd, thanks very much for those kind comments. It...Todd, thanks very much for those kind comments. It's always very encouraging to get feedback like that. I am, as it happens, working on a book, at very early stages so far, and hope to have some time to really work on it sometime soon. Just working on cloning myself first!Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-27323443872517092302013-03-26T08:34:07.812-07:002013-03-26T08:34:07.812-07:00I agree - the classification scheme used is clearl...I agree - the classification scheme used is clearly arbitrary in many respects. There is evidence that disorders like schizophrenia and autism do have some validity, in that cluster analyses show a non-random clustering of symptoms. However, it is equally clear that these categories overlap other clinical categories in many respects(certainly for individual symptoms) and that their etiology is highly overlapping.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-71339285963536405292013-03-26T02:56:14.717-07:002013-03-26T02:56:14.717-07:00This comment has been removed by a blog administrator.kaviyahttps://www.blogger.com/profile/02297373795488679612noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-77933190197009971482013-03-25T09:36:58.426-07:002013-03-25T09:36:58.426-07:00excellent review and insights - thanks. i agree wi...excellent review and insights - thanks. i agree with your explanation for the observations of wide range of phenotypes. i also think that part of problem with explaining the range of symptoms is taxonomy. we classify diseases (for those we don't have molecular conformation) according to their symptoms hence there are many overlaps. if we saw these conditions as a continuum of expressions of modified functions, model would fit well.Ayse Tezcanhttps://www.blogger.com/profile/05426599272504558855noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-35980330726232030222013-03-24T09:47:09.643-07:002013-03-24T09:47:09.643-07:00This is one of the best pieces I've ever read ...This is one of the best pieces I've ever read on development. It is wide-ranging, conceptual, accessible, and yet technically deep enough to have real meat to it. Reading this makes me hope that you are working on a book that expands on your thinking! You have a rare and welcome combination expository ability and deep expertise. Todd I. Starkhttps://www.blogger.com/profile/02231844857877577527noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-22777901212373359572013-03-22T23:02:15.563-07:002013-03-22T23:02:15.563-07:00Some setting on your page keeps me from zooming th...Some setting on your page keeps me from zooming the text larger.Keithhttps://www.blogger.com/profile/00582893674403399773noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-92087974945468900882013-03-22T01:24:06.183-07:002013-03-22T01:24:06.183-07:00Yes, that may be a good way to think about it - al...Yes, that may be a good way to think about it - almost like seizing is what the brain "wants" to do and it has to be actively prevented from doing so all the time. Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-22410340296800756582013-03-22T01:21:12.179-07:002013-03-22T01:21:12.179-07:00You're absolutely right - the attractor metaph...You're absolutely right - the attractor metaphor works best for clear distinctions. But if you think about the attractor landscape as being shaped by a person's particular genome (and other factors), then the exact phenotypes that emerge (including the severity) are easier to accommodate. (Throw a good dash of chance in the mix and the range of ultimate phenotypes is not so surprising).Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-83689886795040915772013-03-21T14:34:37.139-07:002013-03-21T14:34:37.139-07:00Jim Ranck, my post-doc advisor, used to say, "...Jim Ranck, my post-doc advisor, used to say, "its amazing that brains don't go into seizure all of the time" meaning that its hard to maintain cerebral cortex in an active, but not hyperactive state. This way of thinking about it makes the 'emergent' state of a seizure not so surprising. If there are many road-blocks to a seizing cortex, eliminating any one of them may be sufficient. JohnKubiehttps://www.blogger.com/profile/07016323326143767989noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-81001703038714064872013-03-21T14:33:09.564-07:002013-03-21T14:33:09.564-07:00This is a great post on the emergent properties of...This is a great post on the emergent properties of mental states. I'm going to keep the jet analogy in mind for the next time I get into an argument about the materialism of consciousness at a party. ;) I do have one question, though: How do you account for the wide range in severity of mental phenotypes using your "attractor" model? Are Aspergers and severe autism different troughs in the epigenetic landscape? What about life-altering OCD vs. moderate counting and cleaning obsessions? Your explanation works neatly in the case of "all or nothing" diseases, but I think you'll agree that mental states are not so black and white.Gabriellehttps://www.blogger.com/profile/12182860539786850245noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-41935909776590502502013-03-21T07:34:11.116-07:002013-03-21T07:34:11.116-07:00Thanks too to Uta and Chris Frith, David McConnell...Thanks too to Uta and Chris Frith, David McConnell, Dan Bradley and Jackie Dolan for feedback on this piece.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-83204874478442007892013-03-21T06:47:56.658-07:002013-03-21T06:47:56.658-07:00I should have said, many thanks to Partha Mitra fo...I should have said, many thanks to Partha Mitra for his critical comments on my initially undefined use of the term emergent. Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.com