@article{4e0981a736984759bd3e985a4afb8876,
title = "The novel lncRNA lnc-NR2F1 is proneurogenic and mutated in human neurodevelopmental disorders",
abstract = "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.",
author = "Ang, {Cheen Euong} and Qing Ma and Wapinski, {Orly L.} and Shenghua Fan and Flynn, {Ryan A.} and Lee, {Qian Yi} and Bradley Coe and Masahiro Onoguchi and Olmos, {Victor Hipolito} and Do, {Brian T.} and Lynn Dukes-Rimsky and Jin Xu and Koji Tanabe and Liangjiang Wang and Ulrich Elling and Penninger, {Josef M.} and Yang Zhao and Kun Qu and Eichler, {Evan E.} and Anand Srivastava and Marius Wernig and Chang, {Howard Y.}",
note = "Funding Information: We thank Cindy Skinner, Mrs. Sydney Ladd, Dr. Barbra R DuPont, Dr. Katie R Clarkson for patient recruitment and evaluation and members of our labs for discussion and advice. We thank the Stanford Functional Genomic Facility especially Vanita for her assistant in the project. This project is supported by NIH RC4-NS073015 (HYC, MW), P50-HG007735 (HYC), California Institute for Regenerative Medicine (MW, HYC), NIH R01 HD39331 (AKS) and Self Regional Healthcare Foundation Funds (AKS). CEA was supported by California Institute of Regenerative Medicine Training Grant and Siebel Foundation. QM was supported by Stanford Dean{\textquoteright}s Fellowship. OLW was supported by a NSF fellowship. MW is a NYSCF–Robertson Stem Cell Investigator. Haplobank is generously funded by Nestl{\'e} Institute of Health Science NIHS as well as the Austrian National Bank (OeNB) and Era of Hope/National Coalition against Breast Cancer/DoD. UE is supported by the Austrian Academy of Sciences, the Austrian National Bank (OeNB), and is a Wittgenstein Prize fellow. JMP is supported by an Advanced ERC grant and an Era of Hope/DoD grant. MW is an Howard Hughes Medical Institute Faculty Scholar. HYC and EE are Investigators of the Howard Huges Medical Institute. Funding Information: We thank Cindy Skinner, Mrs. Sydney Ladd, Dr. Barbra R DuPont, Dr. Katie R Clarkson for patient recruitment and evaluation and members of our labs for discussion and advice. We thank the Stanford Functional Genomic Facility especially Vanita for her assistant in the project. This project is supported by NIH RC4-NS073015 (HYC, MW), P50-HG007735 (HYC), California Institute for Regenerative Medicine (MW, HYC), NIH R01 HD39331 (AKS) and Self Regional Healthcare Foundation Funds (AKS). CEA was supported by California Institute of Regenerative Medicine Training Grant and Siebel Foundation. QM was supported by Stanford Dean?s Fellowship. OLW was supported by a NSF fellowship. MW is a NYSCF?Robertson Stem Cell Investigator. Haplobank is generously funded by Nestl? Institute of Health Science NIHS as well as the Austrian National Bank (OeNB) and Era of Hope/National Coalition against Breast Cancer/DoD. UE is supported by the Austrian Academy of Sciences, the Austrian National Bank (OeNB), and is a Wittgenstein Prize fellow. JMP is supported by an Advanced ERC grant and an Era of Hope/DoD grant. MW is an Howard Hughes Medical Institute Faculty Scholar. HYC and EE are Investigators of the Howard Huges Medical Institute. Publisher Copyright: {\textcopyright} Ang et al.",
year = "2019",
doi = "10.7554/ELIFE.41770",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}