scholarly journals Link Between Increased Prevalence of Autism Spectrum Disorder Syndromes and Oxidative Stress, DNA Methylation, and Imprinting

2015 ◽  
Vol 169 (11) ◽  
pp. 1066 ◽  
Author(s):  
Yves J. R. Menezo ◽  
Kay Elder ◽  
Brian Dale
Keyword(s):  
Oxidative Stress ◽  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
And Oxidative Stress

scholarly journals LINE-1 and Alu methylation Signatures in Autism Spectrum Disorder and Their Function in The Regulation of Autism-Related Genes

2021 ◽  
Author(s):  
Thanit Saeliw ◽  
Tiravut Permpoon ◽  
Nutta Iadsee ◽  
Tewin Tencomnao ◽  
Tewarit Sarachana ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Autism Spectrum ◽  
Small Sample ◽  
Spectrum Disorder ◽  
Post Mortem ◽  
Global Methylation ◽  
Post Mortem Brain ◽  
Dna Methylation Profiling ◽  
Methylation Profiling

Abstract BackgroundLong interspersed nucleotide element-1 (LINE-1) and Alu elements are retrotransposons whose abilities cause abnormal gene expression and genomic instability. Several studies have focused on DNA methylation profiling of gene regions, but the locus-specific methylation of LINE-1 and Alu elements has not been identified in autism spectrum disorder (ASD).MethodsHere, DNA methylation age was predicted using Horvath’s method. We interrogated locus- and family-specific methylation profiles of LINE-1 and Alu elements (22,352 loci) in ASD blood using publicly-available Illumina Infinium 450K methylation datasets from heterogeneous ASD (n = 52), ASD with 16p11.2 del (n = 7), and ASD with Chromodomain Helicase DNA-binding 8 (CHD8) variants (n = 15). The differentially methylated positions of LINE-1 and Alu elements corresponding to genes were combined with transcriptome data from multiple ASD studies. ROC curve was conducted to examine the specificity of target loci.ResultsEpigenetic age acceleration was significantly decelerated in ASD children over the age of 11 years. DNA methylation profiling revealed LINE-1 and Alu methylation signatures in each ASD risk loci by which global methylation were notably hypomethylated exclusively in ASD with CHD8 variants. When LINE-1 and Alu elements were clustered into subfamilies, we found methylation changes in a family-specific manner in L1P, L1H, HAL, AluJ, and AluS families in the heterogeneous ASD and ASD with CHD8 variants. Our results showed that LINE-1 and Alu methylation within target genes is inversely related to the expression level in each ASD variant. Moreover, LINE-1 and Alu methylation signatures can be used to predict ASD individuals from non-ASD.LimitationsIntegration of methylome and transcriptome datasets was performed from different ASD cohorts. The small sample size of the validation cohort used post-mortem brain tissues and necessitates future validation in a larger cohort.ConclusionsThe DNA methylation signatures of the LINE-1 and Alu elements in ASD, as well as their functional impact on ASD-related genes, have been studied. These findings are considered for further research into DNA methylation profiles and the expression of the LINE-1 and Alu elements in post-mortem brain tissue, which has been linked to ASD pathogenesis.

scholarly journals DNA Methylation and Susceptibility to Autism Spectrum Disorder

2019 ◽  
Vol 70 (1) ◽  
pp. 151-166 ◽  
Author(s):  
Martine W. Tremblay ◽  
Yong-hui Jiang
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Causative Factor ◽  
Autism Spectrum ◽  
Postnatal Period ◽  
Spectrum Disorder ◽  
Regulation Of Transcription ◽  
Peak Time ◽  
Genome Wide ◽  
Technical Advances

The prevalence of autism spectrum disorder (ASD) has been increasing steadily over the last 20 years; however, the molecular basis for the majority of ASD cases remains unknown. Recent advances in next-generation sequencing and detection of DNA modifications have made methylation-dependent regulation of transcription an attractive hypothesis for being a causative factor in ASD etiology. Evidence for abnormal DNA methylation in ASD can be seen on multiple levels, from genetic mutations in epigenetic machinery to loci-specific and genome-wide changes in DNA methylation. Epimutations in DNA methylation can be acquired throughout life, as global DNA methylation reprogramming is dynamic during embryonic development and the early postnatal period that corresponds to the peak time of synaptogenesis. However, technical advances and causative evidence still need to be established before abnormal DNA methylation and ASD can be confidently associated.

scholarly journals ESSENTIAL ELEMENTS IN THE ETIOLOGY AND PATHOGENESIS OF AUTISM SPECTRUM DISORDER IN CHILDREN

2020 ◽  
Vol 21 (4) ◽  
pp. 32-39
Author(s):  
L.N. Chernova ◽  
Keyword(s):  
Oxidative Stress ◽  
Autism Spectrum Disorder ◽  
Central Nervous System ◽  
Nervous System ◽  
Autism Spectrum ◽  
Essential Elements ◽  
Nerve Fibers ◽  
Spectrum Disorder ◽  
Epileptiform Discharges ◽  
Antioxidant Defense Systems

A large number of studies have been conducted up to date associated with the elemental status of children with Autism Spectrum Disorder (ASD). However, it is still difficult to fully explain the relationship between ASD and elements due to previous inconsistent scientific results. The article reviews the possible role of essential elements in the etiopathogenesis of ASD in children. An imbalance of essential elements can cause a disruption in development of central nervous system. It leads to impaired differentiation and proliferation of neurons and disruption in myelination, affects neurochemistry and neurotransmitter balance, provokes oxidative stress and neuroinflammation. In particular, the balance of trace elements such as copper, iron and selenium is necessary to maintain the antioxidant defense systems. Increased levels of free radicals lead to cellular damage, oxidative stress and neuroinflammation linked to ASD. Magnesium and calcium, acting as secondary messengers in the central nervous system (CNS), regulate the processes of neural networks’ maturation and neurotransmitter release. An imbalance of potassium and sodium changes electrical activity of the brain and may be the cause of epileptiform discharges in ASD. Zinc provides the processes of neuronal migration and neurotransmission, while copper, iodine and iron contribute to myelination of nerve fibers.

scholarly journals DNA methylation of PGC-1α is associated with elevated mtDNA copy number and altered urinary metabolites in Autism Spectrum Disorder

2021 ◽  
Author(s):  
Sophia Bam ◽  
Erin Buchanan ◽  
Caitlyn Mahony ◽  
Colleen O’Ryan
Keyword(s):  
Autism Spectrum Disorder ◽  
Dna Methylation ◽  
Mitochondrial Dysfunction ◽  
Copy Number ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Peroxisome Proliferator ◽  
Mtdna Copy Number ◽  
Cpg Sites ◽  
Mtdna Deletions

AbstractBackgroundAutism Spectrum Disorder (ASD) is a complex disorder that is underpinned by numerous dysregulated biological pathways, including canonical mitochondrial pathways. Epigenetic mechanisms contribute to this dysregulation and DNA methylation is an important factor in the aetiology of ASD. We examined the relationship between DNA methylation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), an essential transcriptional regulator of mitochondrial homeostasis, and mitochondrial dysfunction in an ASD cohort of South African children.ResultsUsing targeted Next Generation bisulfite sequencing, we found 12 highly variable CpG sites in PGC-1α that were significantly differentially methylated (p<0.05) between ASD (n = 55) and controls (n = 44). In ASD, eight CpG sites were hypermethylated in the PGC-1α promotor with a putative binding site for CAMP response binding element 1 (CREB1) spanning one of these CpG sites (p = 1 × 10−6). Mitochondrial DNA (mtDNA) copy number, a marker of mitochondrial function, was elevated (p = 0.002) in ASD compared to controls and correlated significantly with DNA methylation at the PGC-1α promoter. There was a positive correlation between methylation at PGC-1α at CpG#1 and mtDNA copy number (Spearman’s r = 0.2, n = 49, p = 0.04) in ASD, but a negative correlation between methylation at PGC-1α at CpG#4 promoter and mtDNA copy number in controls (Spearman’s r = −0.4, n = 42, p = 0.045). While there was no relationship between mtDNA deletions and PGC-1α methylation in ASD, mtDNA deletions correlated negatively with methylation at PGC-1α at CpG#4 (Spearman’s r = −0.4, n = 42, p = 0.032) in controls. Furthermore, levels of urinary organic acids associated with mitochondrial dysfunction correlated significantly (p<0.05) with DNA methylation at PGC-1α CpG#1 and mtDNA copy number in ASD (n= 20) and controls (n= 13) with many of these metabolites involved in altered redox homeostasis and neuroendocrinology.ConclusionsThese data show an association between PGC-1α promoter methylation, elevated mtDNA copy number and metabolomic evidence of mitochondrial dysfunction in ASD. This highlights an unexplored link between DNA methylation and mitochondrial dysfunction in ASD.

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