Convergence of genes and cellular pathways dysregulated in autism spectrum disorders
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/2278 |
Resumo: | 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. |
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Convergence of genes and cellular pathways dysregulated in autism spectrum disordersPerturbações do Desenvolvimento Infantil e Saúde MentalRare copy-number variationAutism Spectrum DisordersAutismRare 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.ElsevierRepositório Científico do Instituto Nacional de SaúdePinto, D.Delaby, E.Merico, D.Barbosa, M.Merikangas, A.Klei, LThiruvahindrapuram, 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.CChiocchetti, 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.2014-05-23T11:02:23Z2014-052014-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/2278engAm J Hum Genet. 2014 May 1;94(5):677-94. doi: 10.1016/j.ajhg.2014.03.018. Epub 2014 Apr 240002-9297doi: 10.1016/j.ajhg.2014.03.018.info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:39:12Zoai:repositorio.insa.pt:10400.18/2278Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:37:18.900894Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
title |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
spellingShingle |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders Pinto, D. Perturbações do Desenvolvimento Infantil e Saúde Mental Rare copy-number variation Autism Spectrum Disorders Autism |
title_short |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
title_full |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
title_fullStr |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
title_full_unstemmed |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
title_sort |
Convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
author |
Pinto, D. |
author_facet |
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. |
author_role |
author |
author2 |
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. |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
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. |
dc.subject.por.fl_str_mv |
Perturbações do Desenvolvimento Infantil e Saúde Mental Rare copy-number variation Autism Spectrum Disorders Autism |
topic |
Perturbações do Desenvolvimento Infantil e Saúde Mental Rare copy-number variation Autism Spectrum Disorders Autism |
description |
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. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-05-23T11:02:23Z 2014-05 2014-05-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/2278 |
url |
http://hdl.handle.net/10400.18/2278 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Am J Hum Genet. 2014 May 1;94(5):677-94. doi: 10.1016/j.ajhg.2014.03.018. Epub 2014 Apr 24 0002-9297 doi: 10.1016/j.ajhg.2014.03.018. |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799132107751030784 |