Abstract
Many studies have demonstrated a robust statistical overlap between genes whose transcripts are reported as Fragile X Mental Retardation Protein (Fmrp)-binding targets and genes implicated in various psychiatric disorders, including autism. However, it is not clear how to interpret this overlap as the Fmrp protein itself is not considered to be central to all instances of these conditions. We tested whether Fmrp binding may be a proxy for some other features of these transcripts. Reviewing recent literature on the cross-linking and immunoprecipitation (CLIP)-derived targets of Fmrp in the brain, and the literature on identifying genes thought to mediate autism and other psychiatric disorders, reveals that both appear to be disproportionately made up of highly brain-expressed genes. This suggests a parsimonious explanation-that the overlap between Fmrp targets and neuropsychiatric candidate genes might be secondary to simple features such as transcript length and robust expression in the brain. Indeed, reanalyzing Fmrp high-throughput sequencing of RNAs isolated by CLIP (HITS-CLIP) data suggests that approximately 60% of CLIP tag depth can be predicted by gene expression, coding sequence length, and transcript length. Furthermor...Continue Reading
References
Aug 1, 1993·Nature Genetics·D DevysJ L Mandel
Jul 26, 2011·Cell·Jennifer C DarnellRobert B Darnell
Sep 26, 2012·Nature Neuroscience·Giles S H Yeo, Lora K Heisler
Dec 14, 2012·Nature·Manuel AscanoThomas Tuschl
May 30, 2013·Nature Genetics·UNKNOWN GTEx Consortium
Dec 10, 2013·Nucleic Acids Research·Danielle WelterHelen Parkinson
Jan 28, 2014·Nature·Shaun M PurcellPamela Sklar
May 27, 2014·Nature Genetics·Mohammed UddinStephen W Scherer
May 31, 2014·Human Molecular Genetics·Joshua A SuhlStephen T Warren
Aug 5, 2014·Nature Genetics·Kaitlin E SamochaMark J Daly
Aug 8, 2014·Nature·Shahar Shohat, Sagiv Shifman
Nov 5, 2014·Nature·Ivan IossifovMichael Wigler
Citations
Oct 27, 2015·Frontiers in Genetics·Nathan KoppJoseph D Dougherty
Nov 18, 2015·Molecular Psychiatry·A ThaparP Holmans
Apr 5, 2016·Cell·Aoife C McMahonMichael Rosbash
Jun 19, 2016·Proceedings of the National Academy of Sciences of the United States of America·Aoife C McMahon, Michael Rosbash
Oct 23, 2016·Behavior Genetics·Erez TsurIdan Menashe
Apr 8, 2016·PloS One·Ya WenMartha R Herbert
Dec 9, 2017·Frontiers in Aging Neuroscience·Roman SmidakGert Lubec
Aug 18, 2018·Science·Sameer Aryal, Eric Klann
Apr 27, 2019·Autism Research : Official Journal of the International Society for Autism Research·Emily L CasanovaManuel F Casanova
Dec 9, 2015·Genes, Brain, and Behavior·Camron D Bryant, Neema Yazdani
Jul 9, 2017·Genome Medicine·Sara Ballouz, Jesse Gillis
Jun 16, 2018·Neurology. Genetics·John K L WongStacey S Cherny
Feb 14, 2017·Frontiers in Molecular Neuroscience·Jasbir S DalalJoseph D Dougherty
Aug 15, 2018·Nature Communications·Ayush T RamanZhandong Liu
Jan 6, 2018·Molecular Psychiatry·Hao HuHossein Najmabadi
Nov 14, 2018·Frontiers in Psychiatry·Emily L CasanovaFrank Alex Feltus
Oct 21, 2020·Molecular Psychiatry·Nicholas E CliftonAndrew J Pocklington
Dec 29, 2020·Cell Reports·Michael A RiegerJoseph D Dougherty
Apr 29, 2021·Proceedings of the National Academy of Sciences of the United States of America·Sameer AryalEric Klann
Jul 15, 2021·ELife·Jasbir Singh DalalMustafa Sahin
Oct 24, 2015·Genes & Development·Daniel J AraujoGenevieve Konopka