Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder

Detalhes bibliográficos
Autor(a) principal: Marques, Ana Rita
Data de Publicação: 2022
Outros Autores: Santos, João Xavier, Martiniano, Hugo, Vilela, Joana, Rasga, Célia, Romão, Luísa, Vicente, Astrid Moura
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/8290
Resumo: This article belongs to the Special Issue mRNA Metabolism in Health and Disease
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spelling Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum DisorderAutism Spectrum DisorderNonsense-mediated mRNA decaySingle Nucleotide VariantsCopy Number VariantsPerturbações do Desenvolvimento Infantil e Saúde MentalAutismoExpressão GénicaGenómica Funcional e EstruturalThis article belongs to the Special Issue mRNA Metabolism in Health and DiseaseAutism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition with unclear etiology. Many genes have been associated with ASD risk, but the underlying mechanisms are still poorly understood. An important post-transcriptional regulatory mechanism that plays an essential role during neurodevelopment, the Nonsense-Mediated mRNA Decay (NMD) pathway, may contribute to ASD risk. In this study, we gathered a list of 46 NMD factors and regulators and investigated the role of genetic variants in these genes in ASD. By conducting a comprehensive search for Single Nucleotide Variants (SNVs) in NMD genes using Whole Exome Sequencing data from 1828 ASD patients, we identified 270 SNVs predicted to be damaging in 28.7% of the population. We also analyzed Copy Number Variants (CNVs) from two cohorts of ASD patients (N = 3570) and discovered 38 CNVs in 1% of cases. Importantly, we discovered 136 genetic variants (125 SNVs and 11 CNVs) in 258 ASD patients that were located within protein domains required for NMD. These gene variants are classified as damaging using in silico prediction tools, and therefore may interfere with proper NMD function in ASD. The discovery of NMD genes as candidates for ASD in large patient genomic datasets provides evidence supporting the involvement of the NMD pathway in ASD pathophysiology.This research was supported by Fundação para a Ciência e a Tecnologia (UIDB/04046/2020 and UIDP/04046/2020 Centre grants to BioISI and PAC-POCI-01-0145-FEDER-016428 MEDPERSYST to A.M.V.) and by National Institute of Health Doutor Ricardo Jorge. A.R.M., J.V. and J.X.S. are recipients of a fellowship from BioSys PhD programme PD65-2012 (A.R.M. Ref: PD/BD/113773/2015; J.X.S. Ref: PD/BD/114386/2016; J.V. Ref: PD/BD/131390/2017) from Fundação para a Ciência e a Tecnologia (Portugal).MDPIRepositório Científico do Instituto Nacional de SaúdeMarques, Ana RitaSantos, João XavierMartiniano, HugoVilela, JoanaRasga, CéliaRomão, LuísaVicente, Astrid Moura2022-10-31T15:00:41Z2022-03-132022-03-13T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/8290engBiomedicines. 2022 Mar 13;10(3):665. doi: 10.3390/biomedicines100306652227-905910.3390/biomedicines10030665info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:27Zoai:repositorio.insa.pt:10400.18/8290Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:53.456017Repositório 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 Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
title Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
spellingShingle Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
Marques, Ana Rita
Autism Spectrum Disorder
Nonsense-mediated mRNA decay
Single Nucleotide Variants
Copy Number Variants
Perturbações do Desenvolvimento Infantil e Saúde Mental
Autismo
Expressão Génica
Genómica Funcional e Estrutural
title_short Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
title_full Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
title_fullStr Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
title_full_unstemmed Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
title_sort Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder
author Marques, Ana Rita
author_facet Marques, Ana Rita
Santos, João Xavier
Martiniano, Hugo
Vilela, Joana
Rasga, Célia
Romão, Luísa
Vicente, Astrid Moura
author_role author
author2 Santos, João Xavier
Martiniano, Hugo
Vilela, Joana
Rasga, Célia
Romão, Luísa
Vicente, Astrid Moura
author2_role 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 Marques, Ana Rita
Santos, João Xavier
Martiniano, Hugo
Vilela, Joana
Rasga, Célia
Romão, Luísa
Vicente, Astrid Moura
dc.subject.por.fl_str_mv Autism Spectrum Disorder
Nonsense-mediated mRNA decay
Single Nucleotide Variants
Copy Number Variants
Perturbações do Desenvolvimento Infantil e Saúde Mental
Autismo
Expressão Génica
Genómica Funcional e Estrutural
topic Autism Spectrum Disorder
Nonsense-mediated mRNA decay
Single Nucleotide Variants
Copy Number Variants
Perturbações do Desenvolvimento Infantil e Saúde Mental
Autismo
Expressão Génica
Genómica Funcional e Estrutural
description This article belongs to the Special Issue mRNA Metabolism in Health and Disease
publishDate 2022
dc.date.none.fl_str_mv 2022-10-31T15:00:41Z
2022-03-13
2022-03-13T00:00:00Z
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/10400.18/8290
url http://hdl.handle.net/10400.18/8290
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biomedicines. 2022 Mar 13;10(3):665. doi: 10.3390/biomedicines10030665
2227-9059
10.3390/biomedicines10030665
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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