Non-mendelian genetics/ non-darwinian evolution

People do specifically discuss Mendelian Phenotypes which is misleading because it encourages a correlation to be drawn between your (which I agree with btw) Mendelian Genetics. Unfortunately, like I've already stated this does not hold when you are trying to describe complex diseases. So, for the last time when it comes to complex diseases just because you have gene X does not mean you will have disease X. Therefore, I think this needs to discussed in the coursework of students understanding genetics and the subsequent phenotypes.

Alright, imprint to me means epigenetics. So, I would ask you if you think it is parental OR species inheritance since I think the jury is still out on parental imprinting. In the case of parental imprinting (whether heritable or not) one would still need to consider environment whether it be uterine, nuclear, or ex vivo (antigens). So, in fact I would agree with Ook on this as being a non-Darwinian factor. On the other hand, I would say that it does not contradict mendelian genetics, but that it is supplemental.

I don't fully get your argument - your post seems to contradict itself.Again, what you describe does not violate Mendelian laws, which are unrelated to penetrance and expressivity. The mode by which gene X is inherited is entirely Mendelian, unless you show distortion of segregation. Whether or not gene X leads to a disease is a matter separate of Mendelian law.You repeatedly state that you have problems with the misleading (mis)education of the public regarding genetics. But it seems to me that you are being misleading by using Mendelian laws to describe phenotypic inheritance.

It has been with experimental interspecific Peromyscus crosses between monogamous species and polygamous species with different imprinting.Depending on the direction of the cross, the pups are either growth retarded or grow so large that they cause problems for the mother; which is the prediction from a sexual genome competition that would be unique to the polygamous species. Of note - the authors seem to define Mendelian inheritance at the level of expression; and, they suggest that changes in regulation of imprinting possibly contributed to reproductive isolation.This message has been edited by pink sasquatch, 10-25-2004 04:31 PM

Since you like to hear yourself I will answer you with your very own statements which simply re-state what I have been trying to say from the beginning, but apparently you won't stop until you have said everything, so here you go:Here's my statement in the form of your question: I would interject that traits is equivalent to phenotypes.Here's my answer in the form of your statement: Excuse you! Really? Are you trying to be clever? Remember this: Whew, there for a second I wasn't sure if you thought phenotype was independent of genotype or not especially since you were taking the liberty of telling me I am the one who is misleading. You're right, I guess some would equate complex diseases to the "highly polygenic trait" of height! Give me a break.

Perhaps this is the gist of the problem - you've "been trying to say", but haven't actually done so. Just because you know what you mean when you write something doesn't mean that someone else will. Maybe this is why I thought you were being "misleading" - perhaps you were miscommunicating, since it seems you're now saying "this is what I meant all along."I've looked over your reply to me, and honestly it doesn't really make any sense. All I can tell is that you are frustrated and think you've "got me" in my own statements. I don't see how, and your rants don't help me to see how.My summary of the overall argument:
- You complain that genetics education is misleading.
- You imply that Mendelian genetics fails in regards to complex disease genetics, because of gene-network and gene-environment interactions.
- I state that variability in phenotype does not violate Mendelian genetics, which deals with inheritance of genes, not phenotypes.
- Your statements continue to imply that complex disease genetics is non-Mendelian because of phenotypic variability.
- I call you on using misleading statements, since you have been complaining about misleading education.
- You say that what I've been saying is what you've been trying to say all along, in not-so-civil terms.
- Discussion ends?

Do you mean that it is unclear whether imprinting is simply a parental effect, similar in operation to maternal effect genes setting up initial conditions for the embryos development, or if it is a pattern which is heritable transgenerationally?TTFN,WKP.S. Surely something does not have to contradict mendelian-genetics to be non-mendelian.

Hello Again,Thanks for the links, and for elaborating on what I was trying to say: I tend to over-simplify sometimes. For example:

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To me you seem to be discussing something along the lines of 'evolvability'

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...now that was the word I was looking for! Having said that, I'd like to make an observation about your definitions of epigenetics.I think the reason I like to lump them all together (or at least draw a fuzzy grey line between the two), is that they could share common mechanisms and that those mechanisms (although heritable) are essentially reversable - DNA can get methylated and demethylated, histones can be deacetylated and acetylated.If you imagine a situation where environment caused imprinting to occur, and that imprinting was only partially inherited then this gives a possible source of phenotypic plasticity. Not really backed up by any evidence as such, but maybe a possibility?

Thanks pink sasquatch. I should have known that if there was a subject in imprinting research I did not know much about that Shirley Tilghman had already done the research and published it

Can you clarify this a bit. Do you mean that if an imprinted gene was hypermethylated in the gametes and that methylation was maintained so as to never be expressed then it would be considered some sort of null allele? Even if the actual gene itself was fully functional?On further reflection I see what you mean about the representation in the paper, that mendelian genetics is base on an assumption of equal expression of the 2 inherited alleles. I don't think this is unreasonable in the context of changes within the protein coding regions of a gene, but it obviously falls down somewhat when the source of the allelic variation is within a regulatory region and causes differences in levels of expression itself.I'm not sure if this equivalence of expression levels is really a neccessary feature for menedelian inheritance, although I can see how it works as a simplifying assumption. Ceratinly I can see a distinction between a difference in expression based upon a change in the primary sequence of DNA in a regulatory region and one based upon the hypermethylation of the gene in question.TTFN,WKThis message has been edited by Wounded King, 10-26-2004 08:20 AM

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So, I would ask you if you think it is parental OR species inheritance since I think the jury is still out on parental imprinting.

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I would say parental. I think it is much more likely that two members of the same species share the exact same DNA sequences as opposed to the exact same imprinting pattern. I would expect that an F1 offspring would share the imprinting pattern of its parents but perhaps with more variability than seen at the genetic level i.e. methylation differences accrue more rapidly than DNA sequence differences. But it probably also works under a principle of conservation. Differential methlyation of a non-expressed, non-coding piece of junk DNA is probably tolerable for an organism. But screw up methylation or acetlyation of the Xist locus and it causes major problems.

Sorry about not replying to your earlier post sooner, my typing tends to be as speedy as a sloth on tranqs, so I don't tend to post very much I think this is quite a useful definition to work with. If the amount of non-sequence modification doesn't matter (as in proper 'junk' DNA sections), then it doesn't have to be thought about in relation to evolution/inheritance.If the amount of modification is vital for the gene to function properly then it can be treated for all intents and purposes like a Mendalian allele (but maybe with a little more potential to 'fine-tune' a phenotype). Whether it compliments or antagonises the traditional sequence 'genotype' or not doesn't matter - it is at least 'pseudo-Mendalian'. I think I'm with PS on this one - trying to assign traits to a genome where genes are interacting like crazy is flipping complicated.However, if there are a number of methlylation states which can all be influenced by the environment, and can all give rise to viable (yet differing) phenotypes then the waters can get a bit murky IMO. I agree with an earlier comment of yours: hopefully the Evo-Devo side of things can start to clear things up a bit.Edits: an attempt to make sense This message has been edited by Ooook!, 10-26-2004 11:31 AMThis message has been edited by Ooook!, 10-26-2004 12:08 PM

I have been known to not communicate well.
Let me make ONE MORE attempt, please remember the context.
1) Mendelian genetics, with the understanding that the general public and even many scientists, have is inadequate in promoting understanding and therefore appropriate (targeted approaches) that lead to the comprehensive characterization of complex diseases.....this in no way reflects Pink Sasquatch's level of understanding.
2) The above idea can be illustrated in the fact that a 'Neutral DNA model' is used by some evolutionary scientists to describe how genes have evolved in humans. The problem is that this involves assuming equal contribution by mere presence alone.
3) So, yes, I think that a 'Neutral DNA model' is an inadequate way to describe where we are today in terms of complex diseases. As I, probably unclearly, pointed out I think it is due in part to carrying the ideas of AaBBCcDD=you will be 6 feet tall to cover ALL heritable attributes from our ancestors. It is my opinon that this is flawed when it comes to complex diseases, and could be addressed by encouraging more expansive teaching that incorporates current research endeavors.For everything else you wrote:
Are you suggesting that the general public (WK's "concern" in the first post I thought) and even most scientists have the same level of understanding of genetics as someone with a degree in it? Because you must not have the same access I do to the number of people I can count that directly associate a phenotype with the genotype.....despite you repeating that they are independent.

My best guess is that in common usage you define Mendelian genetics as "using a Punnett square to solve a genetics problem" or perhaps "one-gene = one-trait", whereas I define Mendelian genetics as "a process that does not violate Mendel's laws".Is this a correct assessment? Nope. I don't see why anyone except geneticists needs to understand complex trait genetics.
I don't understand quantum mechanics, or the historical undercurrents that led to the rise and fall of the Russian Empire. Do you? Do we need to?Most human geneticists I know don't even fully understand the complexity and details of the disease process they are mapping modifiers for... Is that a problem?I believe you said you worked on asthma - can you outline all of the biochemical reaction networks that produce the various bronchial constrictor molecules? Show me one single instance where I have said that phenotype and genotype are independent. (It should be easy since I've done it repeatedly.)You do know that "genotype" can refer to the entire genetic make-up of an organism? It only refers to a single locus when it is qualified as such.

1) Yes, in that it could be a species (I hope I have that right) effect. It has been suggested that imprinting is a possible epigenetic explanation for why we are "more evolved", or just plain different, than chimps while still sharing 99% sequence similiarity, as an example. 2) In my opinion, the species imprinting does not in any way preclude parental imprinting in the context you mention above.
3) In contrast, at this point I don't think we can separate the possible pattern of transgenerational heritability and effects on that pattern such as, again, what you suggest above such as maternal effect genes (and many others).I hope I did not parse your question too much.