TY - JOUR T1 - The novel lncRNA <em>lnc-NR2F1</em> is pro-neurogenic and mutated in human neurodevelopmental disorders JF - bioRxiv DO - 10.1101/410837 SP - 410837 AU - Cheen Euong Ang AU - Qing Ma AU - Orly L. Wapinski AU - Shenghua Fan AU - Ryan A. Flynn AU - Bradley Coe AU - Masahiro Onoguchi AU - Victor H. Olmos AU - Brian T. Do AU - Lynn Dukes-Rimsky AU - Jin Xu AU - Qian Yi Lee AU - Koji Tanabe AU - Liangjiang Wang AU - Ulrich Elling AU - Josef Penninger AU - Kun Qu AU - Evan E. Eichler AU - Anand Srivastava AU - Marius Wernig AU - Howard Y. Chang Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/09/08/410837.abstract N2 - Long noncoding RNAs (lncRNAs) have been shown to act as important cell biological regulators including cell fate decisions but are often ignored in human genetics. Combining differential lncRNA expression during neuronal lineage induction with copy number variation morbidity maps of a cohort of children with autism spectrum disorder/intellectual disability versus healthy controls revealed focal genomic mutations affecting several lncRNA candidate loci. Here we find that a t(5:12) chromosomal translocation in a family manifesting neurodevelopmental symptoms disrupts specifically lnc-NR2F1. We further show that lnc-NR2F1 is an evolutionarily conserved lncRNA functionally enhances induced neuronal cell maturation and directly occupies and regulates transcription of neuronal genes including autism-associated genes. Thus, integrating human genetics and functional testing in neuronal lineage induction is a promising approach for discovering candidate lncRNAs involved in neurodevelopmental diseases. ER -