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Autism mutations drive neurodevelopmental pathology

science.org

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Re: Autism mutations drive neurodevelopmental pathology

#31

Post by throw939ii44 »

SubiculumCode wrote: post #6

autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are…

Genetics does not explain steep raise in last a few decades.

Anyway, we do not really know what is causing it, have no real idea what it even is. But we must apply occam's razor very very quickly!

Re: Autism mutations drive neurodevelopmental pathology

#32

Post by SubiculumCode »

s1artibartfast wrote: post #26
SubiculumCode wrote: post #6

autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are…

When autism is discussed as a culmination of denovo mutations, one thing that I dont understand is how this is reconciled with the history of the species. It seems there is a high rate of mutations, making the non-mutant ensemble incredibly fragile. How did this work in the past? Was there significant selection against mutant varieties?

Genetic contributors to autism include:

1. common variants. Common variants are genetic variants weakly associated with autism that we all have to some degree or another, and that only result in autism given a sufficient number of them are found in a person..or at least that's a common idea and pretty well supported. These variants are inherited.

2. rare de novo variants: These are spontaneous genetic variants that the parents did not have, but there was a mutation during production of sperm, for example. Many times, rare de novo variants that occur in highly conserved genes cause tremendous neurodevelopmental problems, spanning death often prenatally, other conditions, and for, autism, most frequently with severe intellectual disability.

Common variants are heritable and common, and are part of the normal spectrum. Only with a very large load do these result in the severest conditions, I think, like intellectual disability.

Occurrence of rare de novo variants are associated with things like age of father (older, less reliable production of sperm without genetic mutations), pesticide exposures, etc.

There is also a real immune factor involved, as well as environmental exposures, which can interact with genes.

Re: Autism mutations drive neurodevelopmental pathology

#33

Post by klipt »

AndrewDucker wrote: post #7
kayo_20211030 wrote: post #2

I'm interested - for reasons. Does anyone have a sense of what this study means in a practical or actionable sense? In toto, the conclusion of the paper: > Together, these findings define a dual-layered model of molecular convergence in ASD: convergence through shared interaction networks in the wild-type state and convergence through recurrent functional consequences of interaction rewiring in the mutant state. More…

Nothing yet. This is incredibly preliminary, with lots of this being tested in frogs. It hopefully gives hints which will be tested,better understood, and show actual mechanisms in humans. But probably not for years.

Dr: I have good news and bad news

Patient: What's the good news?

Dr: We have a two step treatment to improve your social-emotional life.

Patient: What's the bad news?

Dr: The first step is, we have to turn you into a frog...

Re: Autism mutations drive neurodevelopmental pathology

#34

Post by jasonpeacock »

throw939ii44 wrote: post #31
SubiculumCode wrote: post #6

autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are…

Genetics does not explain steep raise in last a few decades. Anyway, we do not really know what is causing it, have no real idea what it even is. But we must apply occam's razor very very quickly!

The steep rise in the last few decades is primarily due to increased awareness and expanded definition/diagnoses.

Re: Autism mutations drive neurodevelopmental pathology

#35

Post by john_strinlai »

throw939ii44 wrote: post #31
SubiculumCode wrote: post #6

autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are…

Genetics does not explain steep raise in last a few decades. Anyway, we do not really know what is causing it, have no real idea what it even is. But we must apply occam's razor very very quickly!

>Genetics does not explain steep raise in last a few decades.

as we built better telescopes, we found more stars

Re: Autism mutations drive neurodevelopmental pathology

#36

Post by sublinear »

SubiculumCode wrote: post #25
roughly wrote: post #12

Earlier quoted context omitted.

Out of curiosity, what leads us to treat ASD as an actual single disorder, as opposed to a billion different individual neurological profiles? I'd expect one of the things that makes this difficult, too, is that there's a missing component of the "machine" - the genetics affect the pathways, which affect (maybe?) things like signal propagation or network regulation in the brain, but the actual effect of that is on th…

A lot of the behaviors by which autism is diagnosed (social communication, repetitive behaviors and restricted interests) are fairly high-level behaviors, dependent on a lot of cognitive/neural machinery beneath it. There is an idea out there that convergent behaviors that allow consistent diagnosis depends on this, as the resulting behaviors might results from differences in many different underlying processes, but…

Is high-level behavior the only criteria for diagnosis?

I think the majority of the public would like to better understand how we came into this position. There's nothing wrong with the topic of autism as research, but it's been a political football for so long that there are many reasonable doubts about methodology, diagnosis, and relevance to everyday healthcare. I understand there may be complications with some patients that require medical diagnosis and intervention, but does that not imply there should be a much more meaningful label on those cases than just the broad umbrella term of "autism"?

On one extreme, we have people thinking they're autistic when they're actually just awkward and inexperienced in life. On the other, we have people with epilepsy who prefer the label "autism" even though they're merely correlated. Something is wrong here. Not with the science, but the discussion.

Re: Autism mutations drive neurodevelopmental pathology

#37

Post by SubiculumCode »

throw939ii44 wrote: post #31
SubiculumCode wrote: post #6

autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are…

Genetics does not explain steep raise in last a few decades. Anyway, we do not really know what is causing it, have no real idea what it even is. But we must apply occam's razor very very quickly!

First, and foremost, the rise in autism rates is due to more sensitive instruments, a broadening of some inclusion criteria between DSM 4 and 5, more awareness of autism, less stigma associated with autism, services attached to autism diagnosis. I believe current research suggests these don't account for all the rise, but does account for most of it.

If I were to include additional biological possibilities, I'd include: a) birth control -> waiting to have children until a later age, more de novo mutations due to age. b) assortive mating, since some careers tend to attract those on the within and on the edges of the spectrum., c) perhaps controversially, and with the very little research on the subject, endocrine disruption from plastic waste exposures.

Re: Autism mutations drive neurodevelopmental pathology

#38

Post by [deleted] »

throw939ii44 wrote: post #31
SubiculumCode wrote: post #6

autism researcher here. I have not yet read this study. It will not be the kind of paper that many, including myself, can read quickly and understand. Autism is a multi-disciplined science, so there is a lot to understand. However, my initial sense from reading the abstract is that this paper might be a really really big deal and incredible new resource. General problem statement: Many different genetic variants are…

Genetics does not explain steep raise in last a few decades. Anyway, we do not really know what is causing it, have no real idea what it even is. But we must apply occam's razor very very quickly!

[deleted]

Re: Autism mutations drive neurodevelopmental pathology

#39

Post by nick__m »

forestrywat wrote: post #11
rickydroll wrote: post #3

Earlier quoted context omitted.

I interpret it as they think they can find treatments that will course-correct the development of a child, but they're not saying anything about fixing something that's already broken.

What do you mean "broken"? Autistic folks are not broken.

There a point on the spectrum where someone cannot function without supervised housing and another one where you have non verbal autistic folks.

But I agree broken is not the right word for those poor folks because they were never functional to begin with!

Re: Autism mutations drive neurodevelopmental pathology

#40

Post by maddie0 »

emptybits wrote: post #13
gignico wrote: post #9

Earlier quoted context omitted.

I thought the US government had just decided that the cause of autism was vaccines

No need for your tag. The United States makes repeated claims linking childhood vaccines to autism. https://www.factcheck.org/2026/08/trump-and-rfk-jr-repeat-fa...

Come now! It is clear that the sarcasm indicator wasn't suggesting that the government didn't really announce that. The sarcasm was in the invocation of governmental authority, which is thereby implied to be ill-founded and not worth listening to.
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