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s1artibartfast an hour ago

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?

SubiculumCode 35 minutes ago | parent | next [-]

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.

s1artibartfast 7 minutes ago | parent [-]

Is there an understanding of the relative prevalence of each type in modern society? Thinking about changing rates of diagnosis, with common circulating variants, it seems like changes to detection and classification would be the only explanation for rate change.

1attice 37 minutes ago | parent | prev [-]

That's a good question with a neat answer: assortive mating can amplify a randomly occurring gene by sexual selection. Read on for the details.

Suppose that there was a gene that made you more likely to be good at white collar thinkwork. You meet your partner at a professional event and have a baby. The baby now has between zero and two copies of the gene. And depending on gene dominance, the probability of at least repeating the ratio of the previous generation is like 75% IIRC.

Repeat, and fold back in. Next generation, you have a couple folks with both mutations, who exhibit an even stronger affinity for quiet thoughtful work (and people). Their kids will have a 100% chance of carrying at least one copy, right? The numbers for the third gen will be even higher.

This is all massively simplified but yeah. Mendel has the answers. The picture is even clearer if you suppose multiple genes whose effects stack, which appears to be the case with the ol 'tism.

And, finally, there is the lived experience of why this happens so much. Speaking as someone on the spec, I could never imagine life partnership with an allistic person, nor can I imagine such a person putting up with my deficiencies and quirks. Moreover, quite literally all my friends are also autspec and would never interface with someone who isn't. So I believe ASD is strongly selected for by people with ASD.

But given the volumes I'd expect we are in the hockey stick armpit of an exponential curve. Like HIV bubbling away in 1950s Africa long before we even had a name for the condition, nineteenth century colonial industrialism probably quietly worked up a stock of the relevant mutations, and the mutants found each other in the grand blender of the 20th century's upheavals.

As it were, silicon valley is one of the precipitants of sex, war, and intellect.