@article{3057148,
    title = "Functional impact of global rare copy number variation in autism spectrum disorders",
    author = "Pinto, D. and Pagnamenta, A.T. and Klei, L. and Anney, R. and Merico, D. and Regan, R. and Conroy, J. and Magalhaes, T.R. and Correia, C. and Abrahams, B.S. and Almeida, J. and Bacchelli, E. and Bader, G.D. and Bailey, A.J. and Baird, G. and Battaglia, A. and Berney, T. and Bolshakova, N. and Bölte, S. and Bolton, P.F. and Bourgeron, T. and Brennan, S. and Brian, J. and Bryson, S.E. and Carson, A.R. and Casallo, G. and Casey, J. and Chung, B.H.Y. and Cochrane, L. and Corsello, C. and Crawford, E.L. and Crossett, A. and Cytrynbaum, C. and Dawson, G. and De Jonge, M. and Delorme, R. and Drmic, I. and Duketis, E. and Duque, F. and Estes, A. and Farrar, P. and Fernandez, B.A. and Folstein, S.E. and Fombonne, E. and Freitag, C.M. and Gilbert, J. and Gillberg, C. and Glessner, J.T. and Goldberg, J. and Green, A. and Green, J. and Guter, S.J. and Hakonarson, H. and Heron, E.A. and Hill, M. and Holt, R. and Howe, J.L. and Hughes, G. and Hus, V. and Igliozzi, R. and Kim, C. and Klauck, S.M. and Kolevzon, A. and Korvatska, O. and Kustanovich, V. and Lajonchere, C.M. and Lamb, J.A. and Laskawiec, M. and Leboyer, M. and Le Couteur, A. and Leventhal, B.L. and Lionel, A.C. and Liu, X.-Q. and Lord, C. and Lotspeich, L. and Lund, S.C. and Maestrini, E. and Mahoney, W. and Mantoulan, C. and Marshall, C.R. and McConachie, H. and McDougle, C.J. and McGrath, J. and McMahon, W.M. and Merikangas, A. and Migita, O. and Minshew, N.J. and Mirza, G.K. and Munson, J. and Nelson, S.F. and Noakes, C. and Noor, A. and Nygren, G. and Oliveira, G. and Papanikolaou, K. and Parr, J.R. and Parrini, B. and Paton, T. and Pickles, A. and Pilorge, M. and Piven, J. and Ponting, C.P. and Posey, D.J. and Poustka, A. and Poustka, F. and Prasad, A. and Ragoussis, J. and Renshaw, K. and Rickaby, J. and Roberts, W. and Roeder, K. and Roge, B. and Rutter, M.L. and Bierut, L.J. and Rice, J.P. and Salt, J. and Sansom, K. and Sato, D. and Segurado, R. and Sequeira, A.F. and Senman, L. and Shah, N. and Sheffield, V.C. and Soorya, L. and Sousa, I. and Stein, O. and Sykes, N. and Stoppioni, V. and Strawbridge, C. and Tancredi, R. and Tansey, K. and Thiruvahindrapduram, B. and Thompson, A.P. and Thomson, S. and Tryfon, A. and Tsiantis, J. and Van Engeland, H. and Vincent, J.B. and Volkmar, F. and Wallace, S. and Wang, K. and Wang, Z. and Wassink, T.H. and Webber, C. and Weksberg, R. and Wing, K. and Wittemeyer, K. and Wood, S. and Wu, J. and Yaspan, B.L. and Zurawiecki, D. and Zwaigenbaum, L. and Buxbaum, J.D. and Cantor, R.M. and Cook, E.H. and Coon, H. and Cuccaro, M.L. and Devlin, B. and Ennis, S. and Gallagher, L. and Geschwind, D.H. and Gill, M. and Haines, J.L. and Hallmayer, J. and Miller, J. and Monaco, A.P. and Nurnberger Jr, J.I. and Paterson, A.D. and Pericak-Vance, M.A. and Schellenberg, G.D. and Szatmari, P. and Vicente, A.M. and Vieland, V.J. and Wijsman, E.M. and Scherer, S.W. and Sutcliffe, J.S. and Betancur, C.",
    journal = "Nature",
    year = "2010",
    volume = "466",
    number = "7304",
    pages = "368-372",
    publisher = "Nature Publishing Group",
    issn = "0028-0836",
    doi = "10.1038/nature09146",
    keywords = "guanosine triphosphatase;  Ras protein, abnormality;  cognition;  enzyme activity;  genomics;  genotype;  heritability;  mental health;  motility;  nervous system disorder, article;  autism;  cell motility;  cell proliferation;  cognitive development;  controlled study;  copy number variation;  gene locus;  genotype;  human;  intellectual impairment;  interpersonal communication;  major clinical study;  priority journal;  social interaction",
    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 1. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability2. Although ASDs are known to be highly heritable ( ∼90%)3, the underlying genetic determinants are still largely unknown.Hereweanalysed 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 ASDand/or intellectual disability (1.69 fold, P=3.4×310-4). 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. © 2010 Macmillan Publishers Limited. All rights reserved."
}