Functional impact of global rare copy number variation in autism spectrum disorders View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-07

AUTHORS

Dalila Pinto, Alistair T. Pagnamenta, Lambertus Klei, Richard Anney, Daniele Merico, Regina Regan, Judith Conroy, Tiago R. Magalhaes, Catarina Correia, Brett S. Abrahams, Joana Almeida, Elena Bacchelli, Gary D. Bader, Anthony J. Bailey, Gillian Baird, Agatino Battaglia, Tom Berney, Nadia Bolshakova, Sven Bölte, Patrick F. Bolton, Thomas Bourgeron, Sean Brennan, Jessica Brian, Susan E. Bryson, Andrew R. Carson, Guillermo Casallo, Jillian Casey, Brian H.Y. Chung, Lynne Cochrane, Christina Corsello, Emily L. Crawford, Andrew Crossett, Cheryl Cytrynbaum, Geraldine Dawson, Maretha de Jonge, Richard Delorme, Irene Drmic, Eftichia Duketis, Frederico Duque, Annette Estes, Penny Farrar, Bridget A. Fernandez, Susan E. Folstein, Eric Fombonne, Christine M. Freitag, John Gilbert, Christopher Gillberg, Joseph T. Glessner, Jeremy Goldberg, Andrew Green, Jonathan Green, Stephen J. Guter, Hakon Hakonarson, Elizabeth A. Heron, Matthew Hill, Richard Holt, Jennifer L. Howe, Gillian Hughes, Vanessa Hus, Roberta Igliozzi, Cecilia Kim, Sabine M. Klauck, Alexander Kolevzon, Olena Korvatska, Vlad Kustanovich, Clara M. Lajonchere, Janine A. Lamb, Magdalena Laskawiec, Marion Leboyer, Ann Le Couteur, Bennett L. Leventhal, Anath C. Lionel, Xiao-Qing Liu, Catherine Lord, Linda Lotspeich, Sabata C. Lund, Elena Maestrini, William Mahoney, Carine Mantoulan, Christian R. Marshall, Helen McConachie, Christopher J. McDougle, Jane McGrath, William M. McMahon, Alison Merikangas, Ohsuke Migita, Nancy J. Minshew, Ghazala K. Mirza, Jeff Munson, Stanley F. Nelson, Carolyn Noakes, Abdul Noor, Gudrun Nygren, Guiomar Oliveira, Katerina Papanikolaou, Jeremy R. Parr, Barbara Parrini, Tara Paton, Andrew Pickles, Marion Pilorge, Joseph Piven, Chris P. Ponting, David J. Posey, Annemarie Poustka, Fritz Poustka, Aparna Prasad, Jiannis Ragoussis, Katy Renshaw, Jessica Rickaby, Wendy Roberts, Kathryn Roeder, Bernadette Roge, Michael L. Rutter, Laura J. Bierut, John P. Rice, Jeff Salt, Katherine Sansom, Daisuke Sato, Ricardo Segurado, Ana F. Sequeira, Lili Senman, Naisha Shah, Val C. Sheffield, Latha Soorya, Inês Sousa, Olaf Stein, Nuala Sykes, Vera Stoppioni, Christina Strawbridge, Raffaella Tancredi, Katherine Tansey, Bhooma Thiruvahindrapduram, Ann P. Thompson, Susanne Thomson, Ana Tryfon, John Tsiantis, Herman Van Engeland, John B. Vincent, Fred Volkmar, Simon Wallace, Kai Wang, Zhouzhi Wang, Thomas H. Wassink, Caleb Webber, Rosanna Weksberg, Kirsty Wing, Kerstin Wittemeyer, Shawn Wood, Jing Wu, Brian L. Yaspan, Danielle Zurawiecki, Lonnie Zwaigenbaum, Joseph D. Buxbaum, Rita M. Cantor, Edwin H. Cook, Hilary Coon, Michael L. Cuccaro, Bernie Devlin, Sean Ennis, Louise Gallagher, Daniel H. Geschwind, Michael Gill, Jonathan L. Haines, Joachim Hallmayer, Judith Miller, Anthony P. Monaco, John I. Nurnberger, Andrew D. Paterson, Margaret A. Pericak-Vance, Gerard D. Schellenberg, Peter Szatmari, Astrid M. Vicente, Veronica J. Vieland, Ellen M. Wijsman, Stephen W. Scherer, James S. Sutcliffe, Catalina Betancur

ABSTRACT

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways. More... »

PAGES

368

Journal

TITLE

Nature

ISSUE

7304

VOLUME

466

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature09146

DOI

http://dx.doi.org/10.1038/nature09146

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012902412

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20531469


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