Repository logo
 
Publication

Autism Spectrum Disorder: contribution of genetic variants involved in the nonsense-mediated mRNA decay

2021-11-18Conference object Restricted access
Simple item page
dc.contributor.authorMarques, Ana Rita
dc.contributor.authorSantos, João Xavier
dc.contributor.authorVilela, Joana
dc.contributor.authorRasga, Célia
dc.contributor.authorMartiniano, Hugo
dc.contributor.authorOliveira, Guiomar
dc.contributor.authorRomão, Luísa
dc.contributor.authorMoura Vicente, Astrid
dc.date.accessioned2022-07-11T16:48:41Z
dc.date.embargo2025-12-31
dc.date.issued2021-11-18
dc.description.abstractIntroduction: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by impairedsocial/communication skills and stereotyped/repetitive behaviors. Genetic factors account for 50-80% of the familialrisk of ASD, but genetic determinants are not fully understood and a role for regulatory processes is plausible. Inthis study, we explored the contribution to ASD etiology of genes involved in an important post-transcriptionalregulatory mechanism implicated in neurodevelopment, the Nonsense-Mediated Decay (NMD). Methods: We first compiled a group of 46 genes encoding NMD factors and regulators. In these genes wesearched for Single Nucleotide Variants (SNVs) and Copy Number Variants (CNVs) in two samples of ASD patients(N=1828 and N=3570, respectively). We observed the frequency of these variants in 60146 controls from gnomADv2.1.1 (for SNVs) and in 10355 controls from the Database of Genomic Variant ( for CNVs). In genes with rarevariants (MAF<1% in controls) predicted to be pathogenic in silico , we further investigated whether these variantsaffect protein domains required for NMD. Results: We identified 270 predicted pathogenic SNVs within 38 genes in 524 ASD patients (28.7% of the total ASDcases) and 38 CNVs located in 18 genes in 38 ASD patients (1% of the ASD cases). Five of these genes, RBM8A , UPF2 , FMR1 , SMG6 and EIF4G1, were previously associated with ASD. We found that 136 variants (122 SNVsand 11 CNVs), in 23 genes, were located within known protein domainsrequired for NMD. These variants, identifiedin 258 ASD patients, may affect proper NMD function and consequently contribute to changes in the expression ofNMD targets. Discussion : In this study we identified genetic variants that may affect NMD function in ASD patients. Since mostNMD targets encode proteins expressed in the brain, we hypothesize that NMD impairment can constitute a riskfactor to ASD pathophysiology. Further studies are needed to better understand the impact of these genetic variantson NMD function and their relevance for ASD.A full understanding of these regulatory mechanisms may constitutean opportunity for the development of therapeutic interventions.pt_PT
dc.description.sponsorshipA.R.Marques is recipient of a fellowship from BioSys PhD programme (Ref PD/BD/113773/2015 from FCT (Portugal).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/8228
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relationAutism Spectrum Disorder ASD: genetic, epigenetic and environmental issues
dc.subjectDoenças Genéticaspt_PT
dc.subjectGenómica Funcionalpt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectPerturbações do Desenvolvimento Infantil e Saúde Mentalpt_PT
dc.subjectAutismopt_PT
dc.subjectAutism Spectrum Disorderpt_PT
dc.titleAutism Spectrum Disorder: contribution of genetic variants involved in the nonsense-mediated mRNA decaypt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleAutism Spectrum Disorder ASD: genetic, epigenetic and environmental issues
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F113773%2F2015/PT
oaire.citation.conferencePlace(online)pt_PT
oaire.citation.title25th Annual Meeting of the Portuguese Society of Human Genetics, 18-19 Novembro 2021pt_PT
person.familyNameRomão
person.givenNameLuísa
person.identifierhttps://scholar.google.pt/citations?hl=pt-PT&user=CAHjIsoAAAAJ&cstart=60&pagesize=20
person.identifier.ciencia-idEB19-DF07-EB37
person.identifier.orcid0000-0002-5061-5287
person.identifier.scopus-author-idhttp://www.scopus.com/authid/detail.url?authorId=6602834878
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isAuthorOfPublicatione2eb8254-24ed-4bfc-b478-3e9022f729e2
relation.isAuthorOfPublication.latestForDiscoverye2eb8254-24ed-4bfc-b478-3e9022f729e2
relation.isProjectOfPublication4f218b20-344a-4d9c-a583-71713852d963
relation.isProjectOfPublication.latestForDiscovery4f218b20-344a-4d9c-a583-71713852d963

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Autism Spectrum Disorder-contribution of genetic variants involved in the nonsense-mediated mRNA decay.pdf
Size:
1.94 MB
Format:
Adobe Portable Document Format
Download

Collections

DGH - Posters/abstracts em congressos internacionais
DPSPDNT - Posters/abstracts em congressos internacionais