PT  - JOURNAL ARTICLE
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
TI  - The novel lncRNA <em>lnc-NR2F1</em> is pro-neurogenic and mutated in human neurodevelopmental disorders
AID  - 10.1101/410837
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 410837
4099  - http://biorxiv.org/content/early/2018/09/08/410837.short
4100  - http://biorxiv.org/content/early/2018/09/08/410837.full
AB  - 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.