scholarly journals Altered DNA Methylation Patterns Associated With Clinically Relevant Increases in PTSD Symptoms and PTSD Symptom Profiles in Military Personnel

2018 ◽  
Vol 20 (3) ◽  
pp. 352-358 ◽  
Author(s):  
Christiana Martin ◽  
Young-Eun Cho ◽  
Hyungsuk Kim ◽  
Sijung Yun ◽  
Rebekah Kanefsky ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Military Personnel ◽  
Axonal Guidance ◽  
Epigenetic Changes ◽  
Ptsd Symptoms ◽  
Cross Sectional ◽  
Canonical Pathways ◽  
Longitudinal Comparison ◽  
Clinical Changes ◽  
Methylation Patterns

Military personnel experience posttraumatic stress disorder (PTSD), which is associated with differential DNA methylation across the whole genome. However, the relationship between these DNA methylation patterns and clinically relevant increases in PTSD severity is not yet clearly understood. The purpose of this study was to identify differences in DNA methylation associated with PTSD symptoms and investigate DNA methylation changes related to increases in the severity of PTSD in military personnel. In this pilot study, a cross-sectional comparison was made between military personnel with PTSD (n = 8) and combat-matched controls without PTSD (n = 6). Symptom measures were obtained, and genome-wide DNA methylation was measured using methylated DNA immunoprecipitation (MeDIP-seq) from whole blood samples at baseline and 3 months later. A longitudinal comparison measured DNA methylation changes in military personnel with clinically relevant increases in PTSD symptoms between time points (PTSD onset) and compared methylation patterns to controls with no clinical changes in PTSD. In military personnel with elevated PTSD symptoms 3 months following baseline, 119 genes exhibited reduced methylation and 8 genes exhibited increased methylation. Genes with reduced methylation in the PTSD-onset group relate to the canonical pathways of netrin signaling, Wnt/Ca+ pathway, and axonal guidance signaling. These gene pathways relate to neurological disorders, and the current findings suggest that these epigenetic changes potentially relate to PTSD symptomology. This study provides some novel insights into the role of epigenetic changes in PTSD symptoms and the progression of PTSD symptoms in military personnel.

scholarly journals Epigenetic aging of human hematopoietic cells is not accelerated upon transplantation into mice

2018 ◽  
Author(s):  
Joana Frobel ◽  
Susann Rahmig ◽  
Julia Franzen ◽  
Claudia Waskow ◽  
Wolfgang Wagner
Keyword(s):  
Dna Methylation ◽  
Epigenetic Clock ◽  
Epigenetic Changes ◽  
Hematopoietic Stem ◽  
Hematopoietic Development ◽  
Immunodeficient Mice ◽  
Epigenetic Aging ◽  
Normal Human ◽  
Methylation Patterns

AbstractTransplantation of human hematopoietic stem cells into immunodeficient mice provides a powerful in vivo model system to gain functional insights into hematopoietic differentiation. So far, it remains unclear if epigenetic changes of normal human hematopoiesis are recapitulated upon engraftment into such “humanized mice”. Mice have a much shorter life expectancy than men, and therefore we hypothesized that the xenogeneic environment might greatly accelerate the epigenetic clock. We demonstrate that genome-wide DNA methylation patterns of normal human hematopoietic development are indeed recapitulated upon engraftment in mice – particularly those of normal early B cell progenitor cells. Furthermore, we tested three epigenetic aging signatures and none of them indicated that the murine environment accelerated age-associated DNA methylation changes. These results demonstrate that the murine transplantation model overall recapitulates epigenetic changes of human hematopoietic development, whereas epigenetic aging seems to occur cell intrinsically.

scholarly journals DNA hyper-methylation associated with schizophrenia may lead to breakdown of self-tolerance

2021 ◽  
Author(s):  
Hui Wei ◽  
Yanbo Yuan ◽  
Caiyun Zhu ◽  
Mingjie Ma ◽  
Fude Yang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genomic Dna ◽  
Target Genes ◽  
Environmental Stressors ◽  
Chinese Han ◽  
Cross Sectional ◽  
Self Tolerance ◽  
Positive Correlations ◽  
Methylation Patterns

Abstract Environmental stressors have effects on the genomic DNA methylation patterns of B lymphocytes in schizophrenia (SCZ), which may therefore perturb the immune homeostasis and trigger autoimmune responses. This study aimed to investigate the global genomic DNA methylation differences in remitters of SCZ (RSCZ) and non-remitters of SCZ (NRSCZ), further their effects on autoimmune responses of target genes. A total of 2722 Chinese Han origin subjects were recruited, including a follow-up cohort and a cross-sectional cohort. We found a DMS of cg14341177 in SCZ which inhibit the mRNA alternative splicing of BICD2, further leading to increased plasma anti-BICD2 IgG autoantibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in the endpoint samples of RSCZ, but not in NRSCZ. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and PANSS scores. These data suggest that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.

DNA methylation profiling identifies epigenetic differences between early versus late stages of diabetic chronic kidney disease

2020 ◽  
Author(s):  
Ashani Lecamwasam ◽  
Boris Novakovic ◽  
Braydon Meyer ◽  
Elif I Ekinci ◽  
Karen M Dwyer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Dna Methylation ◽  
Kidney Disease ◽  
Secretory Protein ◽  
Differentially Methylated Region ◽  
P Value ◽  
Operating Characteristics ◽  
Cross Sectional ◽  
Cpg Sites ◽  
Methylation Patterns

Abstract Background We investigated a cross-sectional epigenome-wide association study of patients with early and late diabetes-associated chronic kidney disease (CKD) to identify possible epigenetic differences between the two groups as well as changes in methylation across all stages of diabetic CKD. We also evaluated the potential of using a panel of identified 5′-C-phosphate-G-3′ (CpG) sites from this cohort to predict the progression of diabetic CKD. Methods This cross-sectional study recruited 119 adults. DNA was extracted from blood using the Qiagen QIAampDNA Mini Spin Kit. Genome-wide methylation analysis was performed using Illumina Infinium MethylationEPIC BeadChips (HM850K). Intensity data files were processed and analysed using the minfi and MissMethyl packages for R. We examined the degree of methylation of CpG sites in early versus late diabetic CKD patients for CpG sites with an unadjusted P-value <0.01 and an absolute change in methylation of 5% (n = 239 CpG sites). Results Hierarchical clustering of the 239 CpG sites largely separated the two groups. A heat map for all 239 CpG sites demonstrated distinct methylation patterns in the early versus late groups, with CpG sites showing evidence of progressive change. Based on our differentially methylated region (DMR) analysis of the 239 CpG sites, we highlighted two DMRs, namely the cysteine-rich secretory protein 2 (CRISP2) and piwi-like RNA-mediated gene silencing 1 (PIWIL1) genes. The best predictability for the two groups involved a receiver operating characteristics curve of eight CpG sites alone and achieved an area under the curve of 0.976. Conclusions We have identified distinct DNA methylation patterns between early and late diabetic CKD patients as well as demonstrated novel findings of potential progressive methylation changes across all stages (1–5) of diabetic CKD at specific CpG sites. We have also identified associated genes CRISP2 and PIWIL1, which may have the potential to act as stage-specific diabetes-associated CKD markers, and showed that the use of a panel of eight identified CpG sites alone helps to increase the predictability for the two groups.

DNA Methylation in Placentas of Interspecies Mouse Hybrids

Genetics ◽  
2003 ◽  
Vol 165 (1) ◽  
pp. 223-228
Author(s):  
Sabine Schütt ◽  
Andrea R Florl ◽  
Wei Shi ◽  
Myriam Hemberger ◽  
Annie Orth ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Basis ◽  
Interspecific Hybrids ◽  
Genetic System ◽  
Differential Methylation ◽  
Late Gestation ◽  
Epigenetic Changes ◽  
Repeat Sequences ◽  
Mouse Placenta ◽  
Methylation Patterns

Abstract Interspecific hybridization in the genus Mus results in several hybrid dysgenesis effects, such as male sterility and X-linked placental dysplasia (IHPD). The genetic or molecular basis for the placental phenotypes is at present not clear. However, an extremely complex genetic system that has been hypothesized to be caused by major epigenetic changes on the X chromosome has been shown to be active. We have investigated DNA methylation of several single genes, Atrx, Esx1, Mecp2, Pem, Psx1, Vbp1, Pou3f4, and Cdx2, and, in addition, of LINE-1 and IAP repeat sequences, in placentas and tissues of fetal day 18 mouse interspecific hybrids. Our results show some tendency toward hypomethylation in the late gestation mouse placenta. However, no differential methylation was observed in hyper- and hypoplastic hybrid placentas when compared with normal-sized littermate placentas or intraspecific Mus musculus placentas of the same developmental stage. Thus, our results strongly suggest that generalized changes in methylation patterns do not occur in trophoblast cells of such hybrids.

Genome flux in tomato auto- and auxo-trophic cell clones cultured in different auxin/cytokinin equilibria. I. DNA multiplicity and methylation levels

Genome ◽  
1995 ◽  
Vol 38 (5) ◽  
pp. 902-912 ◽  
Author(s):  
Patrizia Bogani ◽  
Alessandra Simoni ◽  
Priscilla Bettini ◽  
Maria Mugnai ◽  
M. Gabriella Pellegrini ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Significant Variation ◽  
Physiological State ◽  
Leaf Tissue ◽  
Dna Amplification ◽  
Epigenetic Changes ◽  
Physiological Conditions ◽  
Cell Clones ◽  
Methylation Patterns ◽  
Hormonal Treatments

An analysis of the effect of changing physiological conditions on genetic stability, in terms of epigenetic changes, such as DNA, methylation patterns, and multiplicity of repetitive DNA, was carried out on tomato cell clones grown on media supplemented with different auxin/cytokinin ratios. The effect of endogenous variation in phytohormone equilibria was also indirectly analysed through a comparison of auxotrophic or habituated (autotrophic) cell clones and the differentiated leaf tissue. The data obtained showed significant variation in methylation and multiplicity levels both between clones and between treatments, clearly suggesting a contemporary influence of exogenous hormonal treatments and of the initial/endogenous physiological state of the treated tissue on both phenomena studied.Key words: tomato clones, somaclonal variation, methylation, DNA amplification.

scholarly journals Global DNA Methylation Patterns in Human Gliomas and Their Interplay with Other Epigenetic Modifications

2019 ◽  
Vol 20 (14) ◽  
pp. 3478 ◽  
Author(s):  
Michal J. Dabrowski ◽  
Bartosz Wojtas
Keyword(s):  
Dna Methylation ◽  
Histone Modifications ◽  
Global Gene Expression ◽  
Global Dna Methylation ◽  
Epigenetic Changes ◽  
Human Gliomas ◽  
Human Pathology ◽  
Different Types ◽  
Methylation Patterns ◽  
The Impact

During the last two decades, several international consortia have been established to unveil the molecular background of human cancers including gliomas. As a result, a huge outbreak of new genetic and epigenetic data appeared. It was not only shown that gliomas share some specific DNA sequence aberrations, but they also present common alterations of chromatin. Many researchers have reported specific epigenetic features, such as DNA methylation and histone modifications being involved in tumor pathobiology. Unlike mutations in DNA, epigenetic changes are more global in nature. Moreover, many studies have shown an interplay between different types of epigenetic changes. Alterations in DNA methylation in gliomas are one of the best described epigenetic changes underlying human pathology. In the following work, we present the state of knowledge about global DNA methylation patterns in gliomas and their interplay with histone modifications that may affect transcription factor binding, global gene expression and chromatin conformation. Apart from summarizing the impact of global DNA methylation on glioma pathobiology, we provide an extract of key mechanisms of DNA methylation machinery.

scholarly journals Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of Greek preadolescents

2014 ◽  
Vol 23 (5) ◽  
pp. 654-662 ◽  
Author(s):  
Sarah Voisin ◽  
Markus S Almén ◽  
George Moschonis ◽  
George P Chrousos ◽  
Yannis Manios ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dietary Fat ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Fat Quality ◽  
Genome Wide ◽  
Methylation Patterns

scholarly journals DNA Methylation of TLR4, VEGFA, and DEFA5 Is Associated With Necrotizing Enterocolitis in Preterm Infants

2021 ◽  
Vol 9 ◽  
Author(s):  
Daphne H. Klerk ◽  
Torsten Plösch ◽  
Rikst Nynke Verkaik-Schakel ◽  
Jan B. F. Hulscher ◽  
Elisabeth M. W. Kooi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Epigenetic Changes ◽  
Non Invasive ◽  
Invasive Method ◽  
Observational Cohort ◽  
Stool Samples ◽  
Methylation Patterns ◽  
Short Time

Background: Epigenetic changes, such as DNA methylation, may contribute to an increased susceptibility for developing necrotizing enterocolitis (NEC) in preterm infants. We assessed DNA methylation in five NEC-associated genes, selected from literature: EPO, VEGFA, ENOS, DEFA5, and TLR4 in infants with NEC and controls.Methods: Observational cohort study including 24 preterm infants who developed NEC (≥Bell Stage IIA) and 45 matched controls. DNA was isolated from stool samples and methylation measured using pyrosequencing. We investigated differences in methylation prior to NEC compared with controls. Next, in NEC infants, we investigated methylation patterns long before, a short time before NEC onset, and after NEC.Results: Prior to NEC, only TLR4 CpG 2 methylation was increased in NEC infants (median = 75.4%, IQR = 71.3–83.8%) versus controls (median = 69.0%, IQR = 64.5–77.4%, p = 0.025). In NEC infants, VEGFA CpG 3 methylation was 0.8% long before NEC, increasing to 1.8% a short time before NEC and 2.0% after NEC (p = 0.011; p = 0.021, respectively). A similar pattern was found in DEFA5 CpG 1, which increased from 75.4 to 81.4% and remained 85.3% (p = 0.027; p = 0.019, respectively). These changes were not present for EPO, ENOS, and TLR4.Conclusion: Epigenetic changes of TLR4, VEGFA, and DEFA5 are present in NEC infants and can differ in relation to the time of NEC onset. Differences in DNA methylation of TLR4, VEGFA, and DEFA5 may influence gene expression and increase the risk for developing NEC. This study also demonstrates the use of human DNA extraction from stool samples as a novel non-invasive method for exploring the bowel of preterm infants and which can also be used for necrotizing enterocolitis patients.

scholarly journals Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins

2017 ◽  
Author(s):  
Yunzhang Wang ◽  
Robert Karlsson ◽  
Erik Lampa ◽  
Qian Zhang ◽  
Åsa K. Hedman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Monozygotic Twins ◽  
Cross Sectional ◽  
Age Related ◽  
Genome Wide ◽  
Illumina Humanmethylation450 ◽  
Binding Factor ◽  
Old Swedish ◽  
Methylation Patterns ◽  
Over Time

AbstractAge-related changes in DNA methylation have been observed in many cross-sectional studies, but longitudinal evidence is still very limited. Here, we aimed to characterize longitudinal age-related methylation patterns (Illumina HumanMethylation450 array) using 1011 blood samples collected from 385 old Swedish twins (mean age of 69 at baseline) up to five times over 20 years. We identified 1316 age-associated methylation sites (p<1.3×10−7) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in PIVUS (p<3.9×10−5) and 594 were replicated in LBC (p<5.1×10−5). Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other unannotated transcription factor binding sites. We further investigated genetic influences on methylation (methylation quantitative trait loci) and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased over time, where monozygotic twins had smaller intra-pair differences than dizygotic twins. We show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. Moreover, the changes are under genetic influence, although this effect is independent of age. In addition, inter-individual methylation variations increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.

Sign in / Sign up

Export Citation Format

Share Document