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Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.

Publication ,  Journal Article
Pinto, D; Delaby, E; Merico, D; Barbosa, M; Merikangas, A; Klei, L; Thiruvahindrapuram, B; Xu, X; Ziman, R; Wang, Z; Vorstman, JAS; Regan, R ...
Published in: Am J Hum Genet
May 1, 2014
Published version (DOI) Link to item

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.

Duke Scholars

Geraldine Dawson
Author Geraldine Dawson Psychiatry, Child & Family Mental Health & Community Psychia ...
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Published In

Am J Hum Genet

DOI

10.1016/j.ajhg.2014.03.018

EISSN

1537-6605

Publication Date

May 1, 2014

Volume

94

Issue

5

Start / End Page

677 / 694

Location

United States

Related Subject Headings

  • Sequence Deletion
  • Pedigree
  • Multigene Family
  • Metabolic Networks and Pathways
  • Male
  • Humans
  • Genetics & Heredity
  • Gene Regulatory Networks
  • Female
  • DNA Copy Number Variations
 

Citation

APA
Chicago
ICMJE
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Pinto, D., Delaby, E., Merico, D., Barbosa, M., Merikangas, A., Klei, L., … Scherer, S. W. (2014). Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet, 94(5), 677–694. https://doi.org/10.1016/j.ajhg.2014.03.018
Pinto, Dalila, Elsa Delaby, Daniele Merico, Mafalda Barbosa, Alison Merikangas, Lambertus Klei, Bhooma Thiruvahindrapuram, et al. “Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.” Am J Hum Genet 94, no. 5 (May 1, 2014): 677–94. https://doi.org/10.1016/j.ajhg.2014.03.018.
Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, et al. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet. 2014 May 1;94(5):677–94.
Pinto, Dalila, et al. “Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.” Am J Hum Genet, vol. 94, no. 5, May 2014, pp. 677–94. Pubmed, doi:10.1016/j.ajhg.2014.03.018.
Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L, Thiruvahindrapuram B, Xu X, Ziman R, Wang Z, Vorstman JAS, Thompson A, Regan R, Pilorge M, Pellecchia G, Pagnamenta AT, Oliveira B, Marshall CR, Magalhaes TR, Lowe JK, Howe JL, Griswold AJ, Gilbert J, Duketis E, Dombroski BA, De Jonge MV, Cuccaro M, Crawford EL, Correia CT, Conroy J, Conceição IC, Chiocchetti AG, Casey JP, Cai G, Cabrol C, Bolshakova N, Bacchelli E, Anney R, Gallinger S, Cotterchio M, Casey G, Zwaigenbaum L, Wittemeyer K, Wing K, Wallace S, van Engeland H, Tryfon A, Thomson S, Soorya L, Rogé B, Roberts W, Poustka F, Mouga S, Minshew N, McInnes LA, McGrew SG, Lord C, Leboyer M, Le Couteur AS, Kolevzon A, Jiménez González P, Jacob S, Holt R, Guter S, Green J, Green A, Gillberg C, Fernandez BA, Duque F, Delorme R, Dawson G, Chaste P, Café C, Brennan S, Bourgeron T, Bolton PF, Bölte S, Bernier R, Baird G, Bailey AJ, Anagnostou E, Almeida J, Wijsman EM, Vieland VJ, Vicente AM, Schellenberg GD, Pericak-Vance M, Paterson AD, Parr JR, Oliveira G, Nurnberger JI, Monaco AP, Maestrini E, Klauck SM, Hakonarson H, Haines JL, Geschwind DH, Freitag CM, Folstein SE, Ennis S, Coon H, Battaglia A, Szatmari P, Sutcliffe JS, Hallmayer J, Gill M, Cook EH, Buxbaum JD, Devlin B, Gallagher L, Betancur C, Scherer SW. Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet. 2014 May 1;94(5):677–694.
Journal cover image

Published In

Am J Hum Genet

DOI

10.1016/j.ajhg.2014.03.018

EISSN

1537-6605

Publication Date

May 1, 2014

Volume

94

Issue

5

Start / End Page

677 / 694

Location

United States

Related Subject Headings

  • Sequence Deletion
  • Pedigree
  • Multigene Family
  • Metabolic Networks and Pathways
  • Male
  • Humans
  • Genetics & Heredity
  • Gene Regulatory Networks
  • Female
  • DNA Copy Number Variations