Abstract
The genetics underlying autism spectrum disorder (ASD) are complex. Approximately 3-5% of ASD cases arise from maternally inherited duplications of 15q11.2-q13.1, termed Duplication 15q syndrome (Dup15q). 15q11.2-q13.1 includes the gene UBE3A which is believed to underlie ASD observed in Dup15q syndrome. UBE3A is an E3 ubiquitin ligase that targets proteins for degradation and trafficking, so finding UBE3A substrates and interacting partners is critical to understanding Dup15q ASD. In this study, we take an unbiased genetics approach to identify genes that genetically interact with Dube3a, the Drosophila melanogaster homolog of UBE3A. We conducted an enhancer/suppressor screen using a rough eye phenotype produced by Dube3a overexpression with GMR-GAL4. Using the DrosDel deficiency kit, we identified 3 out of 346 deficiency lines that enhanced rough eyes when crossed to two separate Dube3a overexpression lines, and subsequently identified IA2, GABA-B-R3, and lola as single genes responsible for rough eye enhancement. Using the FlyLight GAL4 lines to express uas-Dube3a + uas-GFP in the endogenous lola pattern, we observed an increase in the GFP signal compared to uas-GFP alone, suggesting a transcriptional co-activation effect of...Continue Reading
References
Jan 16, 1999·Molecular and Cellular Biology·Z NawazB W O'Malley
Feb 13, 2001·The European Journal of Neuroscience·M MezlerK Raming
Sep 27, 2002·Genesis : the Journal of Genetics and Development·Joseph B Duffy
Aug 15, 2006·Human Molecular Genetics·Lawrence T ReiterEthan Bier
Mar 17, 2007·Science·Jonathan SebatMichael Wigler
Jul 16, 2008·Proceedings of the National Academy of Sciences of the United States of America·Barret D PfeifferGerald M Rubin
Jul 19, 2008·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Jihyun KimJeongsil Kim-Ha
Oct 9, 2008·Neurobiology of Disease·Amber HogartN Carolyn Schanen
Apr 15, 2009·Molecular and Cellular Biology·Hyung Cheol Kim, Jon M Huibregtse
Jun 10, 2010·Nature·Dalila PintoCatalina Betancur
Dec 15, 2010·Neuron·David DahdalJustin Blau
Dec 15, 2010·Neurobiology of Disease·Faiza FerdousyLawrence T Reiter
Dec 2, 2011·Neural Development·Michael A GatesEdward Giniger
Mar 27, 2012·Genome Biology·R Kimberley CookKevin R Cook
Oct 10, 2012·Molecular Psychiatry·D Moreno-De-LucaD H Ledbetter
Mar 16, 2013·Autism Research : Official Journal of the International Society for Autism Research·Nora UrracaLawrence T Reiter
Apr 30, 2013·PloS One·Laura JensenLawrence T Reiter
Jun 12, 2013·PLoS Genetics·Hyun Ji NohCaleb Webber
Oct 5, 2013·Molecular Neurobiology·Jimmy El Hokayem, Zafar Nawaz
Nov 21, 2015·Epigenomics·Janine M LaSalleStormy J Chamberlain
Apr 1, 2016·MMWR. Surveillance Summaries : Morbidity and Mortality Weekly Report. Surveillance Summaries·Deborah L ChristensenUNKNOWN Centers for Disease Control and Prevention (CDC)
Apr 5, 2017·Annual Review of Biochemistry·Ning Zheng, Nitzan Shabek
May 16, 2017·American Journal of Human Genetics·Julia WangHugo J Bellen
Jun 28, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Devalkumar J RajyaguruRonald S Go