Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.

Dalila Pinto 1, 2, 3, 4, 5, 6 Elsa Delaby 7 Daniele Merico 8 Mafalda Barbosa 1, 2, 3 Alison Merikangas 9 Lambertus Klei 10 Bhooma Thiruvahindrapuram 8 Xiao Xu 1, 2, 3 Robert Ziman 8 Zhuozhi Wang 8 Jacob Vorstman 11 Ann Thompson 12 Regina Regan 13 Marion Pilorge 7 Giovanna Pellecchia 8 Alistair Pagnamenta 14 Bárbara Oliveira 15 Christian Marshall 8, 16 Tiago Magalhaes 13, 15, 17 Jennifer Lowe 18, 19 Jennifer Howe 8 Anthony Griswold 20 John Gilbert 20 Eftichia Duketis 21 Beth Dombroski 22, 23 Maretha De Jonge 11 Michael Cuccaro 20 Emily Crawford 24, 25 Catarina Correia 15, 26 Judith Conroy 13 Inês Conceição 15 Andreas Chiocchetti 21, 27 Jillian Casey 13 Guiqing Cai 1, 2, 3 Christelle Cabrol 7 Nadia Bolshakova 9 Elena Bacchelli 28 Richard Anney 9 Steven Gallinger 29 Michelle Cotterchio 30 Graham Casey 31 Lonnie Zwaigenbaum 32 Kerstin Wittemeyer 33 Kirsty Wing 14 Simon Wallace 34 Herman Van Engeland 11 Ana Tryfon 2, 3 Susanne Thomson 25, 24 Latha Soorya 2, 3 Bernadette Rogé 35 Wendy Roberts 36 Fritz Poustka 21 Susana Mouga 37, 38 Nancy Minshew 10 Alison Mcinnes 2, 3 Susan Mcgrew 39 Catherine Lord 40 Marion Leboyer 41, 42 Ann Le Couteur 43, 44 Alexander Kolevzon 2, 3, 4, 45 Patricia Jiménez González 46 Suma Jacob 47 Richard Holt 14 Stephen Guter 47 Jonathan Green 48 Andrew Green 13 Christopher Gillberg 49, 50 Bridget Fernandez 51, 52 Frederico Duque 37 Richard Delorme 53 Geraldine Dawson 54 Pauline Chaste 10 Cátia Café 37 Sean Brennan 9 Thomas Bourgeron 53 Patrick Bolton 55, 56 Sven Bölte 21 Raphael Bernier 57 Gillian Baird 58 Anthony Bailey 59, 60 Evdokia Anagnostou 61 Joana Almeida 37 Ellen Wijsman 62, 63 Veronica Vieland 64 Astrid Vicente 15, 17 Gerard Schellenberg 22, 65 Margaret Pericak-Vance 20 Andrew Paterson 8 Jeremy Parr 66, 67 Guiomar Oliveira 37, 38 John Nurnberger 68 Anthony Monaco 14 Elena Maestrini 28 Sabine Klauck 69 Hakon Hakonarson 70, 71 Jonathan Haines 24, 25 Daniel Geschwind 18 Christine Freitag 21 Susan Folstein 20, 72, 73 Sean Ennis 13 Hilary Coon 74 Agatino Battaglia 75 Peter Szatmari 12 James Sutcliffe 24, 25 Joachim Hallmayer 76 Michael Gill 9 Edwin Cook 47, 77 Joseph Buxbaum 1, 2, 3, 4, 5, 78 Bernie Devlin 10 Louise Gallagher 9 Catalina Betancur 7, * Stephen Scherer 8, 16, *
* Auteur correspondant
Abstract : Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.
Type de document :
Article dans une revue
American Journal of Human Genetics, Elsevier (Cell Press), 2014, 94 (5), pp.677-694. 〈10.1016/j.ajhg.2014.03.018〉
Liste complète des métadonnées

Littérature citée [64 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00986225
Contributeur : Catalina Betancur <>
Soumis le : jeudi 1 mai 2014 - 20:51:48
Dernière modification le : mercredi 23 mai 2018 - 17:58:09
Document(s) archivé(s) le : lundi 10 avril 2017 - 18:07:22

Fichiers

Pinto_AGP_CNV_AJHG_2014.pdf
Accord explicite pour ce dépôt


Identifiants

Citation

Dalila Pinto, Elsa Delaby, Daniele Merico, Mafalda Barbosa, Alison Merikangas, et al.. Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders.. American Journal of Human Genetics, Elsevier (Cell Press), 2014, 94 (5), pp.677-694. 〈10.1016/j.ajhg.2014.03.018〉. 〈inserm-00986225〉

Partager

Métriques

Consultations de la notice

14307

Téléchargements de fichiers

1595