newappeal t1_irf95t8 wrote on October 7, 2022 at 4:59 PM

Reply to comment by -Metacelsus- in How common are genetic mutations in conception? by soygang

>for example about 30% of autism cases are caused by de novo mutations

The linked paper appears to say that 30% of de novo mutations in people with ASD contribute to autism, not that 30% of instances of ASD are caused by de novo mutations. In my opinion, the claim they make in the abstract is not the same as the one they make in the paper itself (see page 219, the fourth page of the article, for the 30% figure in context).

-Metacelsus- t1_irfcuu0 wrote on October 7, 2022 at 5:27 PM

Hmm, I re-read that section and I can't quite figure out what they're trying to say. You're right that it seems different from what they say in the abstract. I'll edit my original comment.

Xilon-Diguus t1_irg5mm5 wrote on October 7, 2022 at 9:08 PM

The last I heard (source) the current thinking was that simple repeat expansion was the source of most de novo mutations, leading to phenotypic changes and symptom severity. This isn't really my field so there might have been a more recent update, but I spend enough time dealing with structural changes to the genome that I read this one when it came out.

Repeat expansion doesn't really behave like a classical mutation, and is more a product of an increased likelihood of specific types of error in DNA replication and repair.

regular_modern_girl t1_irg9ndg wrote on October 7, 2022 at 9:41 PM

yeah I was gonna say, I think the exact causes of ASD and autism in general are pretty controversial and somewhat unsettled, particularly the exact way genetics plays a role, and which genes are most likely to be responsible, so unless there’s been some very recent major breakthrough, “30% of ASD cases are caused by de novo mutations” seems a really bold claim, considering that would make de novo mutations one of the most significant contributing causes by far, and at least last I heard, the exact genetic causes of autism were not that settled (and heritable genes were more often thought to play a large role in at least certain types of cases). The former, more conservative claim seems a lot easier to swallow.