Brief Update: What’s New in the Field of Autism Genetics?

Unfortunately this week I’m bogged down with a lot of writing (grant, manuscript revision, etc.) and so my post is going to have to be rather short. But I wanted to take the opportunity to point my readers towards some new research on autism genetics that was published just this last week in Nature. Here are links to the articles below:

De Rubeis et al. Synaptic, transcriptional and chromatin genes disrupted in autism.

Iossifov et al. The contribution of de novo coding mutations to autism spectrum disorder.

So, what’s so important about these articles? Well, as a brief synopsis, the De Rubeis et al. article has very rapidly added to the available pool of potential strong association autism-risk genes by studying a large group of autism simplex cases. So, great for scientists like me: there’s plenty of fodder for future study. The authors also report that of the 107 genes strongly implicated in their cohort, they exhibit loss-of-function mutations in over 5% of the autistic subject but, on the other hand, these same genes tend to be very strongly conserved in evolutionary terms. These same 107 genes also overlapped in functional domains of synaptic transmission, transcriptional regulation, and chromatin remodeling. I’ll discuss in future why this strong conservation (e.g, low recombination rate, strong promoter conservation, strong untranslated region conservation, etc.) is relevant to autism-risk genes, how that might tie into their basic cellular functions, and what roles transposable elements may feasibly play in rare mutations within or near these genes. Some of this will be drawn from my own work, but much of it has already been studied in basic genomics, though is essentially unknown in autism genomics and genetics.

Next, the Iossifov et al. study expounds on our growing understanding that a significant minority of autism cases are strongly influence by rare, highly-penetrant de novo mutations. More importantly, the investigators broke down their analyses by both sex and IQ, and found that coding de novo mutations contribute to 30% of simplex and 45% of female cases. They also found significant overlap in likely gene-disrupting (LGD) targets in females and males with low IQ, but not in males with high IQ. This harkens back to the Jacquemont et al. (2014) study published last spring that indicated that females require a heavier mutational burden in order to reach a similar threshold than males who cross more readily by nature of their sex.

Anyways, enjoy the little snippets, folks. I’m sorry I don’t have more time for blogging this week but I’ll definitely go more in depth on these articles in future. Till next Sunday!

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