Modeling neuronal consequences of autism-associated gene regulatory variants with human induced pluripotent stem cells.
P Joel Ross, Rebecca S F Mok, Brandon S Smith and 4 others
PMID 32398033WHAT IT FOUND
Many autism-associated genetic variants lie outside protein-coding DNA.
Human stem-cell neuron models can test their effects, but what they do in neurons is still unknown.
Key findings
01Protein-coding exons make up less than 2% of the genome, while many autism-associated variants map to non-coding regions.
02Human stem-cell neuron models of autism consistently implicate altered synaptic function, but the direction varies between models.
03The functional consequences of many non-coding variants are still difficult to predict and largely unknown.
STILL TO COME
How it was doneWhat they found
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What it does not show
This is a review of other studies and proposed laboratory methods. Most findings come from stem-cell-derived neurons, animal models, or published laboratory experiments. The functional effects of many non-coding variants are still unknown or hard to predict. Synaptic phenotypes vary between models, so they do not identify one clinical mechanism.
Declared interests
The funding statement names the National Science and Engineering Research Council of Canada, the Canadian Institutes of Health Research, the Simons Foundation Autism Research Initiative, and the University of Toronto McLaughlin Centre. The supplied text does not report author conflicts of interest.
The easy way to misread this
Do not read the stem-cell neuron findings as proof that autism-associated non-coding variants cause synaptic problems in patients. The paper says the functions of these variants remain largely unknown and the models are laboratory approaches.