Skip to main content
Journal cover image

Functional impact of global rare copy number variation in autism spectrum disorders.

Publication ,  Journal Article
Pinto, D; Pagnamenta, AT; Klei, L; Anney, R; Merico, D; Regan, R; Conroy, J; Magalhaes, TR; Correia, C; Abrahams, BS; Almeida, J; Bacchelli, E ...
Published in: Nature
July 15, 2010

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 15, 2010

Volume

466

Issue

7304

Start / End Page

368 / 372

Location

England

Related Subject Headings

  • Social Behavior
  • Signal Transduction
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Gene Dosage
  • Europe
  • DNA Copy Number Variations
  • Cytoprotection
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., … Betancur, C. (2010). Functional impact of global rare copy number variation in autism spectrum disorders. Nature, 466(7304), 368–372. https://doi.org/10.1038/nature09146
Pinto, Dalila, Alistair T. Pagnamenta, Lambertus Klei, Richard Anney, Daniele Merico, Regina Regan, Judith Conroy, et al. “Functional impact of global rare copy number variation in autism spectrum disorders.Nature 466, no. 7304 (July 15, 2010): 368–72. https://doi.org/10.1038/nature09146.
Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature. 2010 Jul 15;466(7304):368–72.
Pinto, Dalila, et al. “Functional impact of global rare copy number variation in autism spectrum disorders.Nature, vol. 466, no. 7304, July 2010, pp. 368–72. Pubmed, doi:10.1038/nature09146.
Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BHY, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu X-Q, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C. Functional impact of global rare copy number variation in autism spectrum disorders. Nature. 2010 Jul 15;466(7304):368–372.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

July 15, 2010

Volume

466

Issue

7304

Start / End Page

368 / 372

Location

England

Related Subject Headings

  • Social Behavior
  • Signal Transduction
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • General Science & Technology
  • Gene Dosage
  • Europe
  • DNA Copy Number Variations
  • Cytoprotection