Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.
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 subjec...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2014
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| _version_ | 1797099238573735936 |
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| author | Pinto, D Delaby, E Merico, D Barbosa, M Merikangas, A Klei, L Thiruvahindrapuram, B Xu, X Ziman, R Wang, Z Vorstman, J Thompson, A Regan, R Pilorge, M Pellecchia, G Pagnamenta, A Oliveira, B Marshall, C Magalhaes, T Lowe, J Howe, J Griswold, A Gilbert, J Duketis, E Dombroski, B |
| author_facet | Pinto, D Delaby, E Merico, D Barbosa, M Merikangas, A Klei, L Thiruvahindrapuram, B Xu, X Ziman, R Wang, Z Vorstman, J Thompson, A Regan, R Pilorge, M Pellecchia, G Pagnamenta, A Oliveira, B Marshall, C Magalhaes, T Lowe, J Howe, J Griswold, A Gilbert, J Duketis, E Dombroski, B |
| author_sort | Pinto, D |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T05:20:54Z |
| format | Journal article |
| id | oxford-uuid:dedd395b-d0e8-41f0-bb5d-560bc511596e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:20:54Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:dedd395b-d0e8-41f0-bb5d-560bc511596e2022-03-27T09:35:18ZConvergence of genes and cellular pathways dysregulated in autism spectrum disorders.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dedd395b-d0e8-41f0-bb5d-560bc511596eEnglishSymplectic Elements at Oxford2014Pinto, DDelaby, EMerico, DBarbosa, MMerikangas, AKlei, LThiruvahindrapuram, BXu, XZiman, RWang, ZVorstman, JThompson, ARegan, RPilorge, MPellecchia, GPagnamenta, AOliveira, BMarshall, CMagalhaes, TLowe, JHowe, JGriswold, AGilbert, JDuketis, EDombroski, BRare 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. |
| spellingShingle | Pinto, D Delaby, E Merico, D Barbosa, M Merikangas, A Klei, L Thiruvahindrapuram, B Xu, X Ziman, R Wang, Z Vorstman, J Thompson, A Regan, R Pilorge, M Pellecchia, G Pagnamenta, A Oliveira, B Marshall, C Magalhaes, T Lowe, J Howe, J Griswold, A Gilbert, J Duketis, E Dombroski, B Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. |
| title | 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_short | Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. |
| title_sort | convergence of genes and cellular pathways dysregulated in autism spectrum disorders |
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