Dna Methylation
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2022 ◽  
Vol 43 ◽  
pp. 111-117
Isabella Lucia Chiara Mariani Wigley ◽  
Eleonora Mascheroni ◽  
Sabrina Bonichini ◽  
Rosario Montirosso

AIDS ◽  
2021 ◽  
Vol 35 (13) ◽  
pp. 2221-2224
Avril Kirsten Moses ◽  
Terisha Ghazi ◽  
Dhaneshree Bestinee Naidoo ◽  
Anil Chuturgoon

2021 ◽  
Vol 13 (1) ◽  
Qingqin S. Li ◽  
Aparna Vasanthakumar ◽  
Justin W. Davis ◽  
Kenneth B. Idler ◽  
Kwangsik Nho ◽  

Abstract Background Identifying biomarkers associated with Alzheimer’s disease (AD) progression may enable patient enrichment and improve clinical trial designs. Epigenome-wide association studies have revealed correlations between DNA methylation at cytosine-phosphate-guanine (CpG) sites and AD pathology and diagnosis. Here, we report relationships between peripheral blood DNA methylation profiles measured using Infinium® MethylationEPIC BeadChip and AD progression in participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Results The rate of cognitive decline from initial DNA sampling visit to subsequent visits was estimated by the slopes of the modified Preclinical Alzheimer Cognitive Composite (mPACC; mPACCdigit and mPACCtrailsB) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) plots using robust linear regression in cognitively normal (CN) participants and patients with mild cognitive impairment (MCI), respectively. In addition, diagnosis conversion status was assessed using a dichotomized endpoint. Two CpG sites were significantly associated with the slope of mPACC in CN participants (P < 5.79 × 10−8 [Bonferroni correction threshold]); cg00386386 was associated with the slope of mPACCdigit, and cg09422696 annotated to RP11-661A12.5 was associated with the slope of CDR-SB. No significant CpG sites associated with diagnosis conversion status were identified. Genes involved in cognition and learning were enriched. A total of 19, 13, and 5 differentially methylated regions (DMRs) associated with the slopes of mPACCtrailsB, mPACCdigit, and CDR-SB, respectively, were identified by both comb-p and DMRcate algorithms; these included DMRs annotated to HOXA4. Furthermore, 5 and 19 DMRs were associated with conversion status in CN and MCI participants, respectively. The most significant DMR was annotated to the AD-associated gene PM20D1 (chr1: 205,818,956 to 205,820,014 [13 probes], Sidak-corrected P = 7.74 × 10−24), which was associated with both the slope of CDR-SB and the MCI conversion status. Conclusion Candidate CpG sites and regions in peripheral blood were identified as associated with the rate of cognitive decline in participants in the ADNI cohort. While we did not identify a single CpG site with sufficient clinical utility to be used by itself due to the observed effect size, a biosignature composed of DNA methylation changes may have utility as a prognostic biomarker for AD progression.

James R. Staley ◽  
Frank Windmeijer ◽  
Matthew Suderman ◽  
Matthew S. Lyon ◽  
George Davey Smith ◽  

AbstractMost studies of continuous health-related outcomes examine differences in mean levels (location) of the outcome by exposure. However, identifying effects on the variability (scale) of an outcome, and combining tests of mean and variability (location-and-scale), could provide additional insights into biological mechanisms. A joint test could improve power for studies of high-dimensional phenotypes, such as epigenome-wide association studies of DNA methylation at CpG sites. One possible cause of heterogeneity of variance is a variable interacting with exposure in its effect on outcome, so a joint test of mean and variability could help in the identification of effect modifiers. Here, we review a scale test, based on the Brown-Forsythe test, for analysing variability of a continuous outcome with respect to both categorical and continuous exposures, and develop a novel joint location-and-scale score (JLSsc) test. These tests were compared to alternatives in simulations and used to test associations of mean and variability of DNA methylation with gender and gestational age using data from the Accessible Resource for Integrated Epigenomics Studies (ARIES). In simulations, the Brown-Forsythe and JLSsc tests retained correct type I error rates when the outcome was not normally distributed in contrast to the other approaches tested which all had inflated type I error rates. These tests also identified > 7500 CpG sites for which either mean or variability in cord blood methylation differed according to gender or gestational age. The Brown-Forsythe test and JLSsc are robust tests that can be used to detect associations not solely driven by a mean effect.

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Changzi Yuan ◽  
Junxia Mao ◽  
Hongyan Sun ◽  
Yiying Wang ◽  
Ming Guo ◽  

Abstract Background Mollusca, a phylum of highly rich species, possess vivid shell colours, but the underlying molecular mechanism remains to be elucidated. DNA methylation, one of the most common epigenetic modifications in eukaryotes, is believed to play a vital role in various biological processes. However, analysis of the effects of DNA methylation on shell colouration has rarely been performed in molluscs, limiting the current knowledge of the molecular mechanism of shell colour formation. Results In the present study, to reveal the role of epigenetic regulation in shell colouration, WGBS, the “gold standard” of DNA methylation analysis, was first performed on the mantle tissues of Yesso scallops (Patinopecten yessoensis) with different shell colours (brown and white), and DNA methylomes at single-base resolution were generated. About 3% of cytosines were methylated in the genome of the Yesso scallop. A slight increase in mCG percentage and methylation level was found in brown scallops. Sequence preference of nearby methylated cytosines differed between high and low methylation level sites and between the brown- and white-shelled scallops. DNA methylation levels varied among the different genomic regions; all the detected regions in the brown group exhibited higher methylation levels than the white group. A total of 41,175 DMRs (differentially methylated regions) were detected between brown and white scallops. GO functions and pathways associated with the biosynthesis of melanin and porphyrins were significantly enriched for DMRs, among which several key shell colour-related genes were identified. Further, different correlations between mRNA expression levels and DNA methylation status were found in these genes, suggesting that DNA methylation regulates shell colouration in the Yesso scallop. Conclusions This study provides genome-wide DNA methylation landscapes of Yesso scallops with different shell colours, offering new insights into the epigenetic regulatory mechanism underlying shell colour.

2021 ◽  
Vol 11 (1) ◽  
Kanako Kojima-Kita ◽  
Satomi Kuramochi-Miyagawa ◽  
Manabu Nakayama ◽  
Haruhiko Miyata ◽  
Steven E. Jacobsen ◽  

AbstractThe PIWI (P-element-induced wimpy testis)-interacting-RNA (piRNA) pathway plays a crucial role in the repression of TE (transposable element) expression via de novo DNA methylation in mouse embryonic male germ cells. Various proteins, including MIWI2 are involved in the process. TE silencing is ensured by piRNA-guided MIWI2 that recruits some effector proteins of the DNA methylation machinery to TE regions. However, the molecular mechanism underlying the methylation is complex and has not been fully elucidated. Here, we identified MORC3 as a novel associating partner of MIWI2 and also a nuclear effector of retrotransposon silencing via piRNA-dependent de novo DNA methylation in embryonic testis. Moreover, we show that MORC3 is important for transcription of piRNA precursors and subsequently affects piRNA production. Thus, we provide the first mechanistic insights into the role of this effector protein in the first stage of piRNA biogenesis in embryonic TE silencing mechanism.

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1622
Eun-Ji Lee ◽  
Myung-Sunny Kim ◽  
Nam-Hui Yim ◽  
Min Ho Cha

The risk factors for stroke, a fatal disease, include type two diabetes, hypertension, and genetic influences. Small vessel occlusion (SVO) can be affected by epigenetic alterations, but an association between SVO and the methylation of cytochrome P450 family 26 subfamily C member 1 (CYP26C1) has not been identified. In this study, we measured the level of DNA methylation in the CYP26C1 promoter and the 5′ untranslated region of 115 normal subjects and 56 patients with SVO in Korea. The DNA methylation level of each subject was measured by bisulfite amplicon sequencing, and statistical analysis was performed using the general linear model or Pearson’s correlation. The average level of DNA methylation was markedly lower in patients with SVO than in normal subjects (20.4% vs. 17.5%). We found that the methylation of CYP26C1 has a significant positive correlation with blood parameters including white blood cells, hematocrit, lactate dehydrogenase, and Na+ in subjects with SVO. We predicted that binding of RXR-α and RAR-β might be affected by CYP26C1 methylation at CpG sites −246–237 and −294–285. These findings suggest that CYP26C1 methylation in the promoter region may be a predictor of SVO.

2021 ◽  
Vol 11 (1) ◽  
Xiaolei Wang ◽  
Jin Huang ◽  
Yixiang Zheng ◽  
Sisi Long ◽  
Huijun Lin ◽  

AbstractGenome-wide DNA methylation profiling have been used to find maternal CpG sites related to the occurrence of gestational diabetes mellitus (GDM). However, none of these differential sites found has been verified in a larger sample. Here, our aim was to evaluate whether first trimester changes in target CpG sites in the peripheral blood of pregnancy women predict subsequent development of GDM. This nested case–control study was based upon an early pregnancy follow-up cohort (ChiCTR1900020652). Target CpG sites were extracted from related published literature and bioinformatics analysis. The DNA methylation levels at 337 CpG sites of 80 GDM cases and 80 matched healthy controls during the early pregnancy (10–15 weeks) were assessed using MethylTarget sequencing. The best cut-off level for methylation of CpG site was determined using the generated ROC curve. The independent effect of CpG site methylation status on GDM was analyzed using conditional logistic regression. Methylation levels at 6 CpG sites were significantly higher in the GDM group than in controls, whereas those at another 6 CpG sites were significantly lower (FDR < 0.05). The area under the ROC curve at each methylation level of the significant CpG sites ranged between 0.593 and 0.650 for the occurrence of GDM. After adjusting for possible confounders, the hypermethylation status of CpG site 68167324 (OR = 3.168, 1.038–9.666) and 24837915 (OR = 5.232, 1.659–16.506) was identified as more strongly associated with GDM; meanwhile, the hypermethylation of CpG site 157130156 (OR = 0.361, 0.135–0.966) and 89438648 (OR = 0.206, 0.065–0.655) might indicate lower risk of GDM. The methylation status of target CpG sites in the peripheral blood of pregnant women during the first trimester may be associated with GDM pathogenesis, and has potential as a predictor of GDM.

Epigenomics ◽  
2021 ◽  
Sonal Saxena ◽  
Sumana Choudhury ◽  
Pranay Amruth Maroju ◽  
Anuhya Anne ◽  
Lov Kumar ◽  

Aim: To study the effects of DNMT1 overexpression on transcript levels of genes dysregulated in schizophrenia and on genome-wide methylation patterns. Materials & methods: Transcriptome and DNA methylome comparisons were made between R1 (wild-type) and Dnmt1tet/tet mouse embryonic stem cells and neurons overexpressing DNMT1. Genes dysregulated in both Dnmt1tet/tet cells and schizophrenia patients were studied further. Results & conclusions: About 50% of dysregulated genes in patients also showed altered transcript levels in Tet/Tet neurons in a DNA methylation-independent manner. These neurons unexpectedly showed genome-wide hypomethylation, increased transcript levels of Tet1 and Apobec 1-3 genes and increased activity and copy number of LINE-1 elements. The observed similarities between Tet/Tet neurons and schizophrenia brain samples reinforce DNMT1 overexpression as a risk factor.

2021 ◽  
Kira A Perzel Mandell ◽  
Nicholas J Eagles ◽  
Amy Deep-Soboslay ◽  
Ran Tao ◽  
Shizhong Han ◽  

Antipsychotic drugs are the current first-line of treatment for schizophrenia and other psychotic conditions. However, their molecular effects on the human brain are poorly studied, due to difficulty of tissue access and confounders associated with disease status. Here we examine differences in gene expression and DNA methylation associated with positive antipsychotic drug toxicology status in the human caudate nucleus. We find no genome-wide significant differences in DNA methylation, but abundant differences in gene expression. These gene expression differences are overall quite similar to gene expression differences between schizophrenia cases and controls. Interestingly, gene expression differences based on antipsychotic toxicology are different between brain regions, potentially due to affected cell type differences. We finally assess similarities with effects in a mouse model, which finds some overlapping effects but many differences as well. As a first look at the molecular effects of antipsychotics in the human brain, the lack of epigenetic effects is unexpected, possibly because long term treatment effects may be relatively stable for extended periods.

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