Reduced transcript expression of genes affected by inherited and de novo CNVs in autism

European Journal of Human Genetics : EJHG
Alex S NordJon M McClellan

Abstract

Individuals with autism are more likely to carry rare inherited and de novo copy number variants (CNVs). However, further research is needed to establish which CNVs are causal and the mechanisms by which these CNVs influence autism. We examined genomic DNA of children with autism (N = 41) and healthy controls (N = 367) for rare CNVs using a high-resolution array comparative genomic hybridization platform. We show that individuals with autism are more likely to harbor rare CNVs as small as ∼ 10 kb, a threshold not previously detectable, and that CNVs in cases disproportionately affect genes involved in transcription, nervous system development, and receptor activity. We also show that a subset of genes that have known or suspected allele-specific or imprinting effects and are within rare-case CNVs may undergo loss of transcript expression. In particular, expression of CNTNAP2 and ZNF214 are decreased in probands compared with their unaffected transmitting parents. Furthermore, expression of PRODH and ARID1B, two genes affected by de novo CNVs, are decreased in probands compared with controls. These results suggest that for some genes affected by CNVs in autism, reduced transcript expression may be a mechanism of pathogenesis dur...Continue Reading

References

Jun 5, 2013·Trends in Neurosciences·Janine M LaSalleDag H Yasui
Oct 16, 2012·Development and Psychopathology·Michael Gill
Jun 26, 2012·Human Molecular Genetics·Brent L FogelDaniel H Geschwind
Aug 9, 2012·Human Molecular Genetics·Giulia FalivelliDavide Comoletti
May 30, 2013·European Journal of Human Genetics : EJHG·Pedro Rodenas-CuadradoSonja C Vernes
Feb 5, 2014·Journal of Neural Transmission·A G ChiocchettiC M Freitag
Jan 15, 2015·Annual Review of Medicine·William M Brandler, Jonathan Sebat
Jan 13, 2016·American Journal of Medical Genetics. Part a·Luisa RonzoniDonatella Milani
Mar 1, 2012·Trends in Molecular Medicine·Olga Peñagarikano, Daniel H Geschwind
Dec 27, 2011·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·A M ManzardoM G Butler
Feb 13, 2015·Intractable & Rare Diseases Research·Joe C H SimPaul J Lockhart
Aug 30, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Tomoki KoshoJohn C Carey
Aug 30, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Gijs W E SantenARID1B-CSS consortium
Sep 10, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Esther Y Son, Gerald R Crabtree
Sep 25, 2014·American Journal of Medical Genetics. Part a·Theodora MalliGerald Webersinke
Jul 31, 2012·Neuroscience and Biobehavioral Reviews·Suzanne CoghlanDavid J Nutt
Oct 5, 2013·Current Opinion in Neurobiology·Brett T Staahl, Gerald R Crabtree
Oct 8, 2013·American Journal of Human Genetics·Caitlin RippeyMary-Claire King
May 28, 2016·Molecular Pharmacology·Pratyush S SuryavanshiShashank M Dravid
Oct 16, 2016·Prenatal Diagnosis·Jiani Yin, Christian P Schaaf
Jan 24, 2017·Trends in Neurosciences·Michisuke Yuzaki, A Radu Aricescu
Jan 9, 2017·Molecular and Cellular Neurosciences·Asami Oguro-AndoJ Peter H Burbach
Sep 5, 2017·International Journal of Molecular Sciences·Mihiro ShibutaniIzuho Hatada
Aug 22, 2017·Frontiers in Molecular Neuroscience·Godwin SokporTran Tuoc
Nov 20, 2019·Translational Psychiatry·Bruna S da SilvaVerônica Contini
May 31, 2017·Professional Case Management·Sarah Armold
Oct 24, 2018·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Pleuntje J van der SluijsGijs W E Santen
Jun 14, 2019·Frontiers in Immunology·Adriana Gata-Garcia, Betty Diamond

Citations

Jan 1, 1995·Psychological Medicine·A BaileyMichael L Rutter
Apr 14, 2000·American Journal of Human Genetics·M AldersM Mannens
Aug 3, 2004·Nature Genetics·A John IafrateCharles Lee
Feb 27, 2007·Nature Genetics·Autism Genome Project ConsortiumKacie J Meyer
Mar 17, 2007·Science·Jonathan SebatMichael Wigler
Jan 9, 2008·American Journal of Human Genetics·Maricela AlarcónDaniel H Geschwind
Jan 11, 2008·The New England Journal of Medicine·L A WeissAutism Consortium
Mar 5, 2008·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Lindsey KentEamonn R Maher
Apr 1, 2008·Biological Psychiatry·Susan L ChristianEdwin H Cook
Apr 17, 2008·Nature Reviews. Genetics·Brett S Abrahams, Daniel H Geschwind
Jul 16, 2008·Science·Eric M MorrowChristopher A Walsh
Oct 9, 2008·Neurobiology of Disease·Amber HogartN Carolyn Schanen
Oct 17, 2008·Nature·Edwin H Cook, Stephen W Scherer
Apr 14, 2009·Human Molecular Genetics·Minori KogaTadao Arinami
May 1, 2009·Nature·Joseph T GlessnerHakon Hakonarson
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Daniel W MeechanAnthony-Samuel LaMantia
Feb 16, 2010·Nature Genetics·Santhosh GirirajanEvan Eichler

Related Concepts

Pathogenic Aspects
ARID1B protein, human
Pathogenesis
Gene Dosage
Transcription, Genetic
CNTNAP2 protein, human
Array-Based Comparative Genomic Hybridization
Autistic Disorder
PRODH gene
ARID1B gene

Related Feeds

Autism

Autism spectrum disorder is associated with challenges with social skills, repetitive behaviors, and often accompanied by sensory sensitivities and medical issues. Here is the latest research.