Next Article in Journal
Novel Biomarkers of Inflammation for the Management of Diabetes: Immunoglobulin-Free Light Chains
Next Article in Special Issue
UPF1 Inhibits Hepatocellular Carcinoma Growth through DUSP1/p53 Signal Pathway
Previous Article in Journal
Structure of Some Green Tea Catechins and the Availability of Intracellular Copper Influence Their Ability to Cause Selective Oxidative DNA Damage in Malignant Cells
Previous Article in Special Issue
New Tricks with Old Dogs: Computational Identification and Experimental Validation of New miRNA–mRNA Regulation in hiPSC-CMs
 
 
Article

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

1
Departamento de Promoção da Saúde e Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal
2
BioISI-Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisboa, Campo Grande, C8, 1749-016 Lisboa, Portugal
3
Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, Avenida Padre Cruz, 1649-016 Lisboa, Portugal
*
Author to whom correspondence should be addressed.
Academic Editor: Faouzi Baklouti
Biomedicines 2022, 10(3), 665; https://doi.org/10.3390/biomedicines10030665
Received: 30 November 2021 / Revised: 4 March 2022 / Accepted: 7 March 2022 / Published: 13 March 2022
(This article belongs to the Special Issue mRNA Metabolism in Health and Disease)
Autism 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. View Full-Text
Keywords: autism spectrum disorder; nonsense-mediated mRNA decay; single nucleotide variants; copy number variants autism spectrum disorder; nonsense-mediated mRNA decay; single nucleotide variants; copy number variants
Show Figures

Figure 1

MDPI and ACS Style

Marques, A.R.; Santos, J.X.; Martiniano, H.; Vilela, J.; Rasga, C.; Romão, L.; Vicente, A.M. Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder. Biomedicines 2022, 10, 665. https://doi.org/10.3390/biomedicines10030665

AMA Style

Marques AR, Santos JX, Martiniano H, Vilela J, Rasga C, Romão L, Vicente AM. Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder. Biomedicines. 2022; 10(3):665. https://doi.org/10.3390/biomedicines10030665

Chicago/Turabian Style

Marques, Ana Rita, João Xavier Santos, Hugo Martiniano, Joana Vilela, Célia Rasga, Luísa Romão, and Astrid Moura Vicente. 2022. "Gene Variants Involved in Nonsense-Mediated mRNA Decay Suggest a Role in Autism Spectrum Disorder" Biomedicines 10, no. 3: 665. https://doi.org/10.3390/biomedicines10030665

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop