Repository logo

Browsing by Author "Magalhães, T.R."

Now showing 1 - 1 of 1
  • Convergence of genes and cellular pathways dysregulated in autism spectrum disorders
    Publication . Pinto, D.; Delaby, E.; Merico, D.; Barbosa, M.; Merikangas, A.; Klei, L; Thiruvahindrapuram, B.; Xu, X.; Ziman, R.; Wang, Z.; Vorstman, J.A.; Thompson, A.; Regan, R.; Pilorge, M.; Pellecchia, G.; Pagnamenta, A.T.; Oliveira, B.; Marshall, C.R.; Magalhães, T.R.; Lowe, J.K.; Howe, J.L.; Griswold, A.J.; Gilbert, J.; Duketis, E.; Dombroski, B.A.; De Jonge, M.V.; Cuccaro, M.; Crawford, E.L.; Correia, C.T.; Conroy, J.; Conceição, I.C; Chiocchetti, A.G.; Casey, J.P.; 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, L.A.; McGrew, S.G.; Lord, C.; Leboyer, M.; Le Couteur, A.S.; Kolevzon, A.; Jiménez González, P.; Jacob, S.; Holt, R.; Guter, S.; Green, J.; Green, A.; Gillberg, C.; Fernandez, B.A.; Duque, F.; Delorme, R.; Dawson, G.; Chaste, P.; Café, C.; Brennan, S.; Bourgeron, T.; Bolton, P.F.; Bölte, S.; Bernier, R.; Baird, G.; Bailey, A.J.; Anagnostou, E.; Almeida, J.; Wijsman, E.M.; Vieland, V.J.; Vicente, A.M.; Schellenberg, G.D.; Pericak-Vance, M.; Paterson, A.D.; Parr, J.R.; Oliveira, G.; Nurnberger, J.I.; Monaco, A.P.; Maestrini, E.; Klauck, S.M.; Hakonarson, H.; Haines, J.L.; Geschwind, D.H.; Freitag, C.M.; Folstein, S.E.; Ennis, S.; Coon, H.; Battaglia, A.; Szatmari, P.; Sutcliffe, J.S.; Hallmayer, J.; Gill, M.; Cook, E.H.; Buxbaum, J.D.; Devlin, B.; Gallagher, L.; Betancur, C.
    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.
    2014-05Journal article Restricted access Show more