Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Autor: Lim, Elaine T., Uddin, Mohammed, De Rubeis, Silvia, Chan, Yingleong, Kamumbu, Anne S., Zhang, Xiaochang, D'Gama, Alissa M., Kim, Sonia N., Hill, Robert Sean, Goldberg, Arthur P., Poultney, Christopher, Minshew, Nancy J., Kushima, Itaru, Aleksic, Branko, Ozaki, Norio, Parellada, Mara, Arango, Celso, Penzol, Maria J., Carracedo, Angel, Kolevzon, Alexander, Hultman, Christina M., Weiss, Lauren A., Fromer, Menachem, Chiocchetti, Andreas G., Freitag, Christine M., Church, George M., Scherer, Stephen W., Buxbaum, Joseph D., Walsh, Christopher A, Aleksic, B, Anney, R, Barbosa, M, Barrett, J, Betancur, C, Bishop, S, Brusco, A, Buxbaum, Jd, Carracedo, A, Chiocchetti, Ag, Chung, Bhy, Cook, E, Coon, H, Cutler, Dj, Daly, M, De Rubeis, S, Doan, R, Fernández-Prieto, M, Ferrero, Gb, Freitag, Cm, Fromer, M, Gargus, J, Geschwind, D, Gill, M, Gómez-Guerrero, L, Hansen-Kiss, E, He, X, Herman, G, Hertz-Picciotto, I, Hultman, C, Iliadou, B, Ionita-Laza, I, Jugessur, A, Knudsen, Gp, Kolevzon, A, Kosmicki, J, Kushima, I, Lee, Sl, Lehner, T, Lennertz, S, Lim, E, Maciel, P, Magnus, P, Manoach, D, Minshew, N, Morrow, E, Mulle, J, Neale, B, Ozaki, N, Palotie, A, Parellada, M, Passos-Bueno, Mr, Pericak-Vance, M, Persico, A, Pessah, I, Reichenberg, A, Reichert, J, Renieri, A, Robinson, E, Samocha, K, Sanders, S, Sandin, S, Santangelo, Sl, Satterstrom, K, Schafer, C, Schellenberg, G, Scherer, S, Senthil, G, Silva, M, Singh, T, Siper, Pm, Soares, G, Stevens, C, Stoltenberg, C, Surén, P, Sutcliffe, Js, Szatmari, P, Tassone, F, Thurm, A, Walsh, C, Weiss, L, Werling, D, Willsey, J, Xu, X, Yu, Tw, Yuen, R, Zwick, Me.
Přispěvatelé: Howard Hughes Medical Institute [Boston] (HHMI), Howard Hughes Medical Institute (HHMI)-Harvard Medical School [Boston] (HMS), Boston Children's Hospital, Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard University [Cambridge], Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Nagoya University, Hospital General Universitario 'Gregorio Marañón' [Madrid], Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Universidade de Santiago de Compostela [Spain] (USC ), CIBER de Enfermedades Raras (CIBERER), Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), King Abdulaziz University, Karolinska Institutet [Stockholm], University of California [San Francisco] (UCSF), University of California, Goethe-University Frankfurt am Main, Génétique de l'autisme = Genetics of Autism (NPS-01), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Hospital for sick children [Toronto] (SickKids), University of Toronto, McLaughlin Centre for Population Health Risk Assessment, University of Ottawa [Ottawa], Autism Sequencing Consortium: Branko Aleksic, Richard Anney, Mafalda Barbosa, Jeffrey Barrett, Catalina Betancur, Somer Bishop, Alfredo Brusco, Joseph D Buxbaum, Angel Carracedo, Andreas G Chiocchetti, Brian H Y Chung, Edwin Cook, Hilary Coon, David J Cutler, Mark Daly, Silvia De Rubeis, Ryan Doan, Montserrat Fernández-Prieto, Giovanni Battista Ferrero, Christine M Freitag, Menachem Fromer, Jay Gargus, Dan Geschwind, Michael Gill, Lorena Gómez-Guerrero, Emily Hansen-Kiss, Xin He, Gail Herman, Irva Hertz-Picciotto, Christina Hultman, Bozenna Iliadou, Iuliana Ionita-Laza, Anil Jugessur, Gun Peggy Knudsen, Alexander Kolevzon, Jack Kosmicki, Itaru Kushima, S L Lee, Thomas Lehner, Savannah Lennertz, Elaine Lim, Patricia Maciel, Per Magnus, Dara Manoach, Nancy Minshew, Eric Morrow, Jennifer Mulle, Benjamin Neale, Norio Ozaki, Aarno Palotie, Mara Parellada, Maria Rita Passos-Bueno, Margaret Pericak-Vance, Antonio Persico, Isaac Pessah, Avi Reichenberg, Jennifer Reichert, Alessandra Renieri, Elise Robinson, Kaitlin Samocha, Stephan Sanders, Sven Sandin, Susan L Santangelo, Kyle Satterstrom, Chad Schafer, Gerry Schellenberg, Stephen Scherer, Geetha Senthil, Marisol Silva, Tarjinder Singh, Paige M Siper, Gabriela Soares, Christine Stevens, Camilla Stoltenberg, Pål Surén, James S Sutcliffe, Peter Szatmari, Flora Tassone, Audrey Thurm, Christopher Walsh, Lauren Weiss, Donna Werling, Jeremy Willsey, Xinyi Xu, Timothy W Yu, Ryan Yuen, Michael E Zwick., University of California [San Francisco] (UC San Francisco), University of California (UC), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Betancur, Catalina
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Proband
Nonsynonymous substitution
Autism Spectrum Disorder
Databases
Genetic
Genetic Predisposition to Disease
Genetic Variation
Humans
Mosaicism
Mutation
Missense
Zygote
Neuroscience (all)
Mutation
Missense
Epigenetics of autism
Biology
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
medicine.disease_cause
Article
03 medical and health sciences
Genetic variation
mental disorders
Databases
Genetic
medicine
Missense mutation
Heritability of autism
MESH: Genetic Variation
MESH: Databases
Genetic
Genetics
MESH: Autism Spectrum Disorder
MESH: Mutation
Missense
[SDV.GEN]Life Sciences [q-bio]/Genetics
MESH: Humans
General Neuroscience
MESH: Genetic Predisposition to Disease
medicine.disease
030104 developmental biology
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Autism spectrum disorder
MESH: Zygote
MESH: Mosaicism
Zdroj: Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Nature Neuroscience
Nature Neuroscience, Nature Publishing Group, 2017, 20 (9), pp.1217-1224. ⟨10.1038/nn.4598⟩
Nature Neuroscience, 2017, 20 (9), pp.1217-1224. ⟨10.1038/nn.4598⟩
Nature neuroscience
ISSN: 1097-6256
1546-1726
Popis: International audience; We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.
Databáze: OpenAIRE
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