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