Elucidating the Spatiotemporal Regulation of a Long Non-Coding RNA Required for Neurodevelopment

PROJECT NARRATIVE The clinical utility of whole genome sequencing to diagnose rare inherited conditions is significantly limited by our inability to interpret variants in the non-coding regions of the genome. This is particularly relevant since misregulation of a relatively new class of non-coding genes, dubbed long non-coding RNAs (lncRNAs), has been implicated in numerous inherited conditions, including neurodevelopmental disorders, but how these genes are normally regulated is understudied. This proposal takes a two-pronged approach to address these limitations through studying the spatiotemporal regulation of a lncRNA that is required for proper neuronal maturation, and by applying statistical genetics-based approaches to curate putative pathogenic non-coding variants in patients with neurodevelopmental disorders.