Repository logo
 
Publication

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

2022-03-13Journal article Open access
Simple item page
dc.contributor.authorMarques, Ana Rita
dc.contributor.authorSantos, João Xavier
dc.contributor.authorMartiniano, Hugo
dc.contributor.authorVilela, Joana
dc.contributor.authorRasga, Célia
dc.contributor.authorRomão, Luísa
dc.contributor.authorVicente, Astrid Moura
dc.date.accessioned2022-10-31T15:00:41Z
dc.date.available2022-10-31T15:00:41Z
dc.date.issued2022-03-13
dc.descriptionThis article belongs to the Special Issue mRNA Metabolism in Health and Diseasept_PT
dc.description.abstractAutism 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.pt_PT
dc.description.sponsorshipThis 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).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiomedicines. 2022 Mar 13;10(3):665. doi: 10.3390/biomedicines10030665pt_PT
dc.identifier.doi10.3390/biomedicines10030665pt_PT
dc.identifier.issn2227-9059
dc.identifier.urihttp://hdl.handle.net/10400.18/8290
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationBiosystems and Integrative Sciences Institute
dc.relationBiosystems and Integrative Sciences Institute
dc.relationAutism Spectrum Disorder ASD: genetic, epigenetic and environmental issues
dc.relationGene- Environment Intereactions in Austim Spectrum Disorders ASD
dc.relationRegulatory RNAs in Autism Spectrum Disorder - modulation of genomic variant effects on clinical phenotype and brain structure and function
dc.relation.publisherversionhttps://www.mdpi.com/2227-9059/10/3/665pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectAutism Spectrum Disorderpt_PT
dc.subjectNonsense-mediated mRNA decaypt_PT
dc.subjectSingle Nucleotide Variantspt_PT
dc.subjectCopy Number Variantspt_PT
dc.subjectPerturbações do Desenvolvimento Infantil e Saúde Mentalpt_PT
dc.subjectAutismopt_PT
dc.subjectExpressão Génica
dc.subjectGenómica Funcional e Estrutural
dc.titleGene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorderpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleBiosystems and Integrative Sciences Institute
oaire.awardTitleAutism Spectrum Disorder ASD: genetic, epigenetic and environmental issues
oaire.awardTitleGene- Environment Intereactions in Austim Spectrum Disorders ASD
oaire.awardTitleRegulatory RNAs in Autism Spectrum Disorder - modulation of genomic variant effects on clinical phenotype and brain structure and function
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04046%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F113773%2F2015/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F114386%2F2016/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F131390%2F2017/PT
oaire.citation.issue3pt_PT
oaire.citation.startPage665pt_PT
oaire.citation.titleBiomedicinespt_PT
oaire.citation.volume10pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStreamOE
oaire.fundingStreamOE
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationdc433369-36fd-4935-bd52-c56aa49c72e1
relation.isProjectOfPublicatione8390b4d-1833-4925-a0ab-5fff0527efaa
relation.isProjectOfPublication4f218b20-344a-4d9c-a583-71713852d963
relation.isProjectOfPublication0415a4cd-2605-4be4-9278-fa7ae7cbfe07
relation.isProjectOfPublication6248bf80-c308-48f9-822e-292782c9cae6
relation.isProjectOfPublication.latestForDiscoverydc433369-36fd-4935-bd52-c56aa49c72e1

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder.pdf
Size:
3.49 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

DPSPDNT - Artigos em revistas internacionais
DGH - Artigos em revistas internacionais