AI Article Synopsis
- The study investigates the role of noncoding regions in autism spectrum disorder (ASD) by analyzing three types: Human Accelerated Regions (HARs), neural Vista Enhancers (VEs), and conserved regions (CNEs).
- It finds that rare inherited variants in these regions are linked to increased ASD risk, especially in families with shared ancestry, suggesting a recessive genetic influence.
- Patient variants identified were shown to affect enhancer activity, highlighting how changes in these noncoding regions may impact social behavior and contribute to ASD risk.
Article Abstract
Little is known about the role of noncoding regions in the etiology of autism spectrum disorder (ASD). We examined three classes of noncoding regions: Human Accelerated Regions (HARs), which show signatures of positive selection in humans; experimentally validated neural Vista Enhancers (VEs); and conserved regions predicted to act as neural enhancers (CNEs). Targeted and whole genome analysis of >16,600 samples and >4900 ASD probands revealed that likely recessive, rare, inherited variants in HARs, VEs, and CNEs substantially contribute to ASD risk in probands whose parents share ancestry, which enriches for recessive contributions, but modestly, if at all, in simplex family structures. We identified multiple patient variants in HARs near and in a VE near and showed that they change enhancer activity. Our results implicate both human-evolved and evolutionarily conserved noncoding regions in ASD risk and suggest potential mechanisms of how changes in regulatory regions can modulate social behavior.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10543033 | PMC |
| http://dx.doi.org/10.1101/2023.09.19.23295780 | DOI Listing |
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