Rare variation in noncoding regions with evolutionary signatures contributes to autism spectrum disorder risk. Rare variation in noncoding regions with evolutionary signatures contributes to autism spectrum disorder risk

We examined three classes of noncoding regions with different patterns of conservation and constraint: Human Accelerated Regions (HARs), which show signatures of positive selection in the human lineage; experimentally validated neural Vista Enhancers (VEs); and candidate neural enhancers (CNEs). We interrogate the in vitro enhancer activity of HARs, VEs, and CNEs in capture-based massively parallel reporter assays (caMPRAs). We also perform random mutagenesis on HARs to assess the effeects of single nucleotide variants on enhancer activity. Overall design: capture-based Massively Parallel Reporter Assays (caMPRAs) of HARs, VEs, and CNEs in the N2A cell line