tag:blogger.com,1999:blog-6146376483374589779.post1108867305981570586..comments2024-02-14T11:18:50.296-08:00Comments on Wiring the Brain: Probabilistic inheritance and neurodevelopmental phenotypes: location, location, locationKevin Mitchellhttp://www.blogger.com/profile/07172255754953214162noreply@blogger.comBlogger13125tag:blogger.com,1999:blog-6146376483374589779.post-13028159743322301942014-03-04T07:51:44.085-08:002014-03-04T07:51:44.085-08:00Look what I found, this is a very informative post...<a href="http://www.alexa.com/siteinfo/badcreditcashadvance.org" rel="nofollow">Look what I found</a>, this is a very informative post. Thanks for I have learned a lot. Hope to see more of your posts. If possible, an article about credit cash would be great. Anonymoushttps://www.blogger.com/profile/05014265414487754042noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-37066597792406920012014-02-06T09:38:31.847-08:002014-02-06T09:38:31.847-08:00The brain is so awesome.The brain is so awesome.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-71555125823614394192013-03-22T14:09:12.331-07:002013-03-22T14:09:12.331-07:00There is definitely so much more research that has...There is definitely so much more research that has to be done here. So many people are suffering from this and need the help here. Unsure what the future brings with it all. <a href="http://www.briankondo.com/" rel="nofollow">Ajax real estate</a>gamefan12https://www.blogger.com/profile/17700305176595632282noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-78646814384793413042012-10-26T03:51:00.877-07:002012-10-26T03:51:00.877-07:00Similar enough at the applicable level of detail t...Similar enough at the applicable level of detail to make circuits that perform within the standard range.<br /><br /><a href="http://www.ukdissertation.co.uk/students_resource/Management_Dissertation.htm" rel="nofollow">management dissertation topics examples</a><br />dissertationconsultanthttps://www.blogger.com/profile/07785686573422414588noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-21818839960183065382012-06-11T16:22:41.881-07:002012-06-11T16:22:41.881-07:00This is a long-shot but I'm new to your blog a...This is a long-shot but I'm new to your blog and I was wondering how I can get you or one of your colleagues to read my post and give me an honest opinion - http://joehefferon.blogspot.com/2012/05/just-dont-call-it-subconscious.html<br /><br />thanks<br />joe hefferonJoe Hefferonhttps://www.blogger.com/profile/17900745825689294102noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-85590585318320980132012-06-06T08:49:28.970-07:002012-06-06T08:49:28.970-07:00Both great examples, thanks.Both great examples, thanks.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-61882369178309685882012-06-06T08:43:35.046-07:002012-06-06T08:43:35.046-07:00Thanks Jon, for great questions. I think the idea ...Thanks Jon, for great questions. I think the idea of some mutations sensitising the system is spot on and many mutations probably act that way. That is certainly the case for many neurodevelopmental systems in model organisms, where that principle has been used directly to screen for additional enhancer or suppressor mutations in order to identify additional components of genetic pathways. And there is growing evidence that many cases of disorders like autism may be due to inheritance of two or more mutations, not just one.<br /><br />A mutation may also make the system more vulnerable to environmental perturbations that can impact neural development. Here, the timing of such insults may indeed have a crucial effect on the phenotypic outcome. <br /><br />These are the kinds of questions that can be addressed empirically in model organisms, where we can directly look at the phenotypic effects of a specific mutation, how variable these are, whether they vary by genetic background and whether they sensitise the system to environmental insults. These parameters are likely to vary with diff mutations - some will have stronger individual effects, others more diffuse.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-23600783308389884782012-06-06T08:39:44.003-07:002012-06-06T08:39:44.003-07:00Great post! Two examples spring to mind:
Mutation...Great post! Two examples spring to mind:<br /><br />Mutations in gene WDR62 <a href="http://neuroskeptic.blogspot.co.uk/2011/11/gene-thats-for-nothing.html" rel="nofollow">are associated with a wide range</a> of severe brain malformations.<br /><br />Exposure of mice to valproate prenatally (which is used as a model of autism amongst other things) causes "patches" of loss of parvalbumin+ GABA interneurons, but the location of these patches varies and some mice show no patches, even if other littermates do: <a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906812/?tool=pubmed" rel="nofollow">ref</a>.Neuroskeptichttps://www.blogger.com/profile/06647064768789308157noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-70846694620131953472012-06-06T08:05:29.895-07:002012-06-06T08:05:29.895-07:00This is great! A couple of thoughts:
1. Should we...This is great! A couple of thoughts:<br /><br />1. Should we just be thinking of genetic factors as having an all or none effect in different (random) locations in the brain? Or is there also scope for genetic factors having a general effect across the whole brain that then leave it more or less vulnerable to a second factor? If so, how would we tell these two apart?<br /><br />Concrete example: Network theory suggests that the brain is generally robust to "insults" because it's highly interconnected - in the same way that it's hard to "take down the internet". But a genetic factor (X) that reduces brain connectivity throughout the brain would then leave it more vulnerable to some secondary insult (eg a de novo mutation). But the effects of that gene X would look exactly the same as the effects of genetic factor Y, which has an all or none effect in random locations in the brain. How do we tell X and Y apart?<br /><br />2. Location, location, location - but also time. The same event could have quite different consequences depending on the point in development at which it occurred. Again, we could think of the same gene being switched on at different points in development and having different consequences. Or the same gene conveying a general vulnerability to other events that could happen at different times.<br /><br />I guess in my naive little brain, something like CNTNAP2 variation might be a good example of something that has a small, general effect on connectivity, but does leave the brain more vulnerable to other stuff - and hence is a risk factor for all kinds of things.drbrocktagonhttps://www.blogger.com/profile/15225859145004971487noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-41286139432831493912012-06-05T23:50:46.076-07:002012-06-05T23:50:46.076-07:00Bhisma - thanks for your comments. My next post wi...Bhisma - thanks for your comments. My next post will be on epigenetics and DNA methylation as a possible source of phenotypic variation. Personally, I think it is a mechanism rather than a source of variation, but I will need a lot more room to expand on that. Whether transgenerational inheritance of DNA methylation is a major factor remains an open question - I have not seen a lot of evidence to suggest that it is, despite examples like the agouti mice.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-69174531270999620742012-06-05T16:38:04.241-07:002012-06-05T16:38:04.241-07:00kevin - thanks for this excellent post. it would b...kevin - thanks for this excellent post. it would be very informative to compare variability due to cellular heterotopia (arising out of 'intrinsic' noise) with more extrinsic factors such as methylation. is there a study that does this comparison directly?<br /><br />@deevybee- the classic case of different phenotypic outcomes for animals of identical genetic background is the agouti mice - where the observable phenotypic difference is entirely due to epigenetic differences laid out early in development. (but this is due to extrinsic/environmental factors and not the intrinsic noise mentioned in the post) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822875/?tool=pubmed<br /><br />Bhisma ChakrabartiAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-14471030518175422862012-06-05T09:21:55.917-07:002012-06-05T09:21:55.917-07:00Thanks for comment and very apt reference. It'...Thanks for comment and very apt reference. It's typical to see range of neuroanatomical phenotypes in experimental animals, which are almost always isogenic. Mutation increases variability, which implies the apparent determinism of wild-type development is really the statistical outcome of thousands of individually probabilistic processes.Kevin Mitchellhttps://www.blogger.com/profile/07172255754953214162noreply@blogger.comtag:blogger.com,1999:blog-6146376483374589779.post-7414010833811312222012-06-05T07:45:42.163-07:002012-06-05T07:45:42.163-07:00Very interested to hear about the examples of vari...Very interested to hear about the examples of variable outcomes in animals of same genotype.<br />In humans, this study of autism in twins is rather similar to your epilepsy example: concordance for autism, but severity can be quite different, even in MZ<br />Le Couteur, A., Bailey, A., Goode, S., Pickles, A., Robertson, S., Gottesman, I., & Rutter, M. (1996). A broader phenotype of autism: the clinical spectrum in twins. Journal of Child Psychology and Psychiatry, 37, 785-802.deevybeehttps://www.blogger.com/profile/15118040887173718391noreply@blogger.com