Evidence for evolution of a key autism-linked gene

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DevilInside
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26 Dec 2010, 2:54 am

i don't follow YOUR crackpot theory ever since i read about it. You don't come across as a scientist but as an autism apologist. Now, the point is, the way we know it's ancestral is because, like explained in the HAR explanation, HAR genes are not remotely as different in other vertebrate lineages. So, since that proves that our gene is different, it implies that whatever AUTS2 regulates was selected for. Also, confusing selection not related to genetic changes increasing or decreaing fitness (always a chanca factor), then you just don't get how evolution works friedmcguffins.

rdos wrote:
DevilInside wrote:
When i was reading about HAR (Human Accelerated Regions) on wikipedia http://en.wikipedia.org/wiki/Human_accelerated_regions, basically genetic regions that are normally conserved throughout vertebrate evolution but strongly changed in the human lineage, suggesting a strong selection pressure for these genes, i noticed that HAR31 (so one of the less significant regions but still significant enough), containted AUTS2, one of the mayor autism susceptibility regions. Some further research showed that the recently sequenced neanderthal genome did NOT have this gene as a HAR, rather the neanderthal genome had a gene copy (allele) much closer to the ancestral chimpanzee-human common ancestor version. So i think this sort of refutes any notion of neanderthal genetics causing autism (although all non-african populations evidently do have a few % neanderthal genes, an important example is 70% of brainsize regulating alleles having come from a neanderthal lineage in non-africans.).


I don't follow your logic.
* Changes to AUTS2 is correlated to autism
* Neanderthals did not have the modern human AUTS2 allele, but a more ancestral form.

How does this prove that Neanderthals did not contribute to the autistic AUTS2 gene? In order to prove the point, we must match the Neanderthal AUTS2 with the autistic AUTS2, which nobody have done AFAIK. It could very well be that autistic AUTS2 is the ancestral state.



rdos
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26 Dec 2010, 3:00 am

ooOoOoOAnaOoOoOoo wrote:
Maybe the neanderthals weren't mutating the way we do.


But it is a mistake to think that all the differences between autistics and neurotypicals are mutations in autistics. If it was so, this would be pretty strange. I think there are just as many cases where neurotypicals mutated and autistics carry the ancestral gene.

Regarding the AUTS2 gene, there is nothing in the linkage studies that suggests that autistics have mutated vs kept the ancestral state. We simply don't know without having the sequences, which are not public AFAIK. At least the autistic sequences are not public. The Neanderthal sequences are.

ooOoOoOAnaOoOoOoo wrote:
One day, we might unlock the door that leads to answers to the many questions about the unique style of human evolution.


There is no unique style of evolution in humans. It all happened in the usual way, whether we like this or not.



rdos
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26 Dec 2010, 3:10 am

DevilInside wrote:
i don't follow YOUR crackpot theory ever since i read about it. You don't come across as a scientist but as an autism apologist. Now, the point is, the way we know it's ancestral is because, like explained in the HAR explanation, HAR genes are not remotely as different in other vertebrate lineages. So, since that proves that our gene is different, it implies that whatever AUTS2 regulates was selected for. Also, confusing selection not related to genetic changes increasing or decreaing fitness (always a chanca factor), then you just don't get how evolution works friedmcguffins.


Cut out the BS, and just present the AUTS2 gene sequence in autistics, neurotypicals and neanderthals below so we can compare them ourself. What you say above has no significance since you haven't explained how the autistic AUTS2 differs from the neurotypical AUTS2 and from the Neanderthal AUTS2.

Also, I did not ask if Neanderthals had the ancestral gene or not (which is beside the point), I asked about HOW THE AUTISTIC AUTS2 LOOKED LIKE.



rdos
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26 Dec 2010, 3:23 am

I don't think that AUTS2 can be used to exclude Neanderthal interbreeding. The difference in AUTS2 in autistics is not a simple mutation, but a duplication. IOW, it is a CNV difference. We don't have the CNV information for Neanderthals.

Reference: http://science.marshall.edu/murraye/444/nature07953.pdf

It is noticable that the above study could not link AUTS2 to ASCs either.



DevilInside
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26 Dec 2010, 3:25 am

neanderthal interbreeding has not been excluded. say, what are the numbers of africans having LESS incidence of autism than eurasians?



DevilInside
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26 Dec 2010, 3:28 am

you are missing my point ENTIRELY if you want to see the specific sequence of the gene in autistics, because changes in a gene that is related to a disorder on a species level might be more informative about the evolutionary background of that disorder than comparing the sequence of a disordered person to a typical person within that population, the point was, this gene has undergone major selection in our lineage, why? why is it related to autism? were the changes related to the autistic brain phenotype?



Cyd
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26 Dec 2010, 4:00 am

I think the NT response to autism is consistent with what would amount to the general population responding to any perceivable move in evolution. And I think that the bearer of such a perceivable change in the area of the brain or mind might perceive the GP as somewhat "backward". Which, I don't know about the rest of you but that's pretty much how I perceive NTs.

Don't get me wrong, I love them to pieces but don't they seem a bit dimwitted? I mean, come on. If we don't empathize with them, we're defective, right? Well, how do they explain their lack of empathy for us? If ours is defective, what makes theirs "normal"? Give me a break. I can't empathize with someone who can't empathize with me. That's what empathy IS, for crying out loud.



rdos
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26 Dec 2010, 4:01 am

DevilInside wrote:
neanderthal interbreeding has not been excluded. say, what are the numbers of africans having LESS incidence of autism than eurasians?


It was several years since I proved the incidence of the Aspie phenotype in afroamericans was about 1/6 of the incidence in other US groups. I recently replicated this finding in a sample close to 100,000.



Last edited by rdos on 26 Dec 2010, 4:11 am, edited 1 time in total.

rdos
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26 Dec 2010, 4:08 am

DevilInside wrote:
you are missing my point ENTIRELY if you want to see the specific sequence of the gene in autistics, because changes in a gene that is related to a disorder on a species level might be more informative about the evolutionary background of that disorder than comparing the sequence of a disordered person to a typical person within that population, the point was, this gene has undergone major selection in our lineage, why? why is it related to autism? were the changes related to the autistic brain phenotype?


There are other examples like this that are not related to brain. Look at the CFTR gene. It has thousands of variants, which means it too has undergone major recent selection.

Why does this happen? Probably because these genes disrupt some other functions. This is a very probable consequence of recent hybridization (with Neanderthal).

In the case of CFTR, we know that certain variants of CFTR causes disease (Cystic Fibrosis), but why are not these variants selected out? Why do the CFTR gene mutate at various points instead of a single functional variant being retained? Possibly because it provide/provided an advantage in combination with other genes. AUTS2 could be similar.

The problem with the AGRE-database, and most of the autism genetic research usign it, is that it compares LFAs with "unaffected siblings", which is not a method we could use to sort out how the Aspie phenotype relates to genetics.



Last edited by rdos on 26 Dec 2010, 4:27 am, edited 1 time in total.

DevilInside
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26 Dec 2010, 4:17 am

i don't understand how you make that last leap?



DevilInside
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26 Dec 2010, 4:20 am

I think we'll have to wait until they publish the whole neanderthal genome in NCBI database so EVERYONE can study the differences and which modern people have more or less neanderthal admixture and if it is at all related to our spectrum incidence.



rdos
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26 Dec 2010, 4:33 am

The Neanderthal DNA sequence is available for free already. You can download it here: http://www.eva.mpg.de/neandertal/data.html

The problem is that the AGRE sequences are not available, nor do we have any full genomes of Aspies.



DevilInside
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26 Dec 2010, 4:41 am

why don't they publish in the NCBI? i never go look anywhere else for genomes



DevilInside
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26 Dec 2010, 4:42 am

aspies? are you excluding autistics from your study?



rdos
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26 Dec 2010, 4:51 am

DevilInside wrote:
aspies? are you excluding autistics from your study?


Not at all, but I'm more intested in the personality-type than mental retardation, and in order to find the source of the personality-type it would be better to exclude people with mental retardation. If I had a few full-genomes of Aspies that score in the "very likely Aspie" range on Aspie-quiz (or above 32 on AQ), I could start to prove / disprove the Neanderthal theory. :wink:



DevilInside
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26 Dec 2010, 4:55 am

*rubs eyes* you didn't really just equate autism = mental retardation and asperger's = autism without mental retardation did you? i'm sure i just misread :)