P.0050 Whole-genome DNA methylation profiles in Anorexia Nervosa: identification of potential epigenetic biomarkers of diagnostic and prognosis

2021 ◽  
Vol 53 ◽  
pp. S36-S37
Author(s):  
N. Ramoz ◽  
J. Clarke ◽  
S. Guillaume ◽  
P. Courtet ◽  
P. Gorwood
Keyword(s):  
Dna Methylation ◽  
Anorexia Nervosa ◽  
Whole Genome ◽  
Epigenetic Biomarkers

FOLLOW-UP STUDY OF WHOLE-GENOME DNA METHYLATION EPIGENETIC PROFILES IN THE REMISSION OF ANOREXIA NERVOSA

2019 ◽  
Vol 29 ◽  
pp. S857
Author(s):  
Nicolas Ramoz ◽  
Sébastien Guillaume ◽  
Philippe Courtet ◽  
Boris Chaumette ◽  
Philip Gorwood
Keyword(s):  
Dna Methylation ◽  
Anorexia Nervosa ◽  
Whole Genome ◽  
Follow Up Study

scholarly journals DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Sasaki ◽  
Margaret E. Eng ◽  
Abigail H. Lee ◽  
Alisa Kostaki ◽  
Stephen G. Matthews
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Guinea Pigs ◽  
Critical Role ◽  
Methylation Status ◽  
Peripheral Tissues ◽  
Epigenetic Biomarkers ◽  
Differentially Methylated Genes ◽  
Increased Risk ◽  
Synthetic Glucocorticoids

AbstractSynthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

scholarly journals Whole-Genome DNA Methylation Analysis in Hydrogen Peroxide Overproducing Transgenic Tobacco Resistant to Biotic and Abiotic Stresses

Plants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 178
Author(s):  
Ana L. Villagómez-Aranda ◽  
Luis F. García-Ortega ◽  
Irineo Torres-Pacheco ◽  
Ramón G. Guevara-González
Keyword(s):  
Hydrogen Peroxide ◽  
Dna Methylation ◽  
Transgenic Tobacco ◽  
Stress Responses ◽  
Abiotic Stresses ◽  
Methylation Status ◽  
Physiological Adaptation ◽  
Whole Genome ◽  
Sequencing Analysis ◽  
Biotic And Abiotic Stresses

Epigenetic regulation is a key component of stress responses, acclimatization and adaptation processes in plants. DNA methylation is a stable mark plausible for the inheritance of epigenetic traits, such that it is a potential scheme for plant breeding. However, the effect of modulators of stress responses, as hydrogen peroxide (H2O2), in the methylome status has not been elucidated. A transgenic tobacco model to the CchGLP gene displayed high H2O2 endogen levels correlated with biotic and abiotic stresses resistance. The present study aimed to determine the DNA methylation status changes in the transgenic model to obtain more information about the molecular mechanism involved in resistance phenotypes. The Whole-genome bisulfite sequencing analysis revealed a minimal impact of overall levels and distribution of methylation. A total of 9432 differential methylated sites were identified in distinct genome regions, most of them in CHG context, with a trend to hypomethylation. Of these, 1117 sites corresponded to genes, from which 83 were also differentially expressed in the plants. Several genes were associated with respiration, energy, and calcium signaling. The data obtained highlighted the relevance of the H2O2 in the homeostasis of the system in stress conditions, affecting at methylation level and suggesting an association of the H2O2 in the physiological adaptation to stress functional linkages may be regulated in part by DNA methylation.

scholarly journals Whole genome DNA methylation: beyond genes silencing

Oncotarget ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 5629-5637 ◽  
Author(s):  
Roberto Tirado-Magallanes ◽  
Khadija Rebbani ◽  
Ricky Lim ◽  
Sriharsa Pradhan ◽  
Touati Benoukraf
Keyword(s):  
Dna Methylation ◽  
Whole Genome

scholarly journals Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles

2020 ◽  
Author(s):  
Benjamin I Laufer ◽  
Hyeyeon Hwang ◽  
Julia M Jianu ◽  
Charles E Mordaunt ◽  
Ian F Korf ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Down Syndrome ◽  
Early Life ◽  
Trisomy 21 ◽  
Bisulfite Sequencing ◽  
Dried Blood Spots ◽  
Whole Genome ◽  
Genome Wide ◽  
Low Pass ◽  
Genome Bisulfite Sequencing

Abstract Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example of genetics shaping epigenetics, as multiple array-based studies have demonstrated that trisomy 21 is characterized by genome-wide alterations to DNA methylation. By assaying over 24 million CpG sites, thousands of genome-wide significant (q < 0.05) differentially methylated regions (DMRs) that distinguished DS from typical development and idiopathic developmental delay were identified. Machine learning feature selection refined these DMRs to 22 loci. The DS DMRs mapped to genes involved in neurodevelopment, metabolism, and transcriptional regulation. Based on comparisons with previous DS methylation studies and reference epigenomes, the hypermethylated DS DMRs were significantly (q < 0.05) enriched across tissues while the hypomethylated DS DMRs were significantly (q < 0.05) enriched for blood-specific chromatin states. A ~28 kb block of hypermethylation was observed on chromosome 21 in the RUNX1 locus, which encodes a hematopoietic transcription factor whose binding motif was the most significantly enriched (q < 0.05) overall and specifically within the hypomethylated DMRs. Finally, we also identified DMRs that distinguished DS NDBS based on the presence or absence of congenital heart disease (CHD). Together, these results not only demonstrate the utility of low-pass WGBS on NDBS samples for epigenome-wide association studies, but also provide new insights into the early life mechanisms of epigenomic dysregulation resulting from trisomy 21.

scholarly journals A Bayesian approach for analysis of whole-genome bisulphite sequencing data identifies disease-associated changes in DNA methylation

2016 ◽  
Author(s):  
Owen J.L. Rackham ◽  
Sarah R. Langley ◽  
Thomas Oates ◽  
Eleni Vradi ◽  
Nathan Harmston ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Promoter Hypermethylation ◽  
Whole Genome ◽  
Sequencing Data ◽  
Accurate Identification ◽  
Bisulphite Sequencing ◽  
Consistent Change ◽  
Rat Strain ◽  
Differential Transcription

ABSTRACTDNA methylation is a key epigenetic modification involved in gene regulation whose contribution to disease susceptibility remains to be fully understood. Here, we present a novel Bayesian smoothing approach (called ABBA) to detect differentially methylated regions (DMRs) from whole-genome bisulphite sequencing (WGBS). We also show how this approach can be leveraged to identify disease-associated changes in DNA methylation, suggesting mechanisms through which these alterations might affect disease. From a data modeling perspective, ABBA has the distinctive feature of automatically adapting to different correlation structures in CpG methylation levels across the genome whilst taking into account the distance between CpG sites as a covariate. Our simulation study shows that ABBA has greater power to detect DMRs than existing methods, providing an accurate identification of DMRs in the large majority of simulated cases. To empirically demonstrate the method’s efficacy in generating biological hypotheses, we performed WGBS of primary macrophages derived from an experimental rat system of glomerulonephritis and used ABBA to identify >1,000 disease-associated DMRs. Investigation of these DMRs revealed differential DNA methylation localized to a 600bp region in the promoter of the Ifitm3 gene. This was confirmed by ChIP-seq and RNA-seq analyses, showing differential transcription factor binding at the Ifitm3 promoter by JunD (an established determinant of glomerulonephritis) and a consistent change in Ifitm3 expression. Our ABBA analysis allowed us to propose a new role for Ifitm3 in the pathogenesis of glomerulonephritis via a mechanism involving promoter hypermethylation that is associated with Ifitm3 repression in the rat strain susceptible to glomerulonephritis.

scholarly journals Whole-Genome Methylation Analysis Revealed ART-Specific DNA Methylation Pattern of Neuro- and Immune-System Pathways in Chinese Human Neonates

2021 ◽  
Vol 12 ◽  
Author(s):  
Zongzhi Liu ◽  
Wei Chen ◽  
Zilong Zhang ◽  
Junyun Wang ◽  
Yi-Kun Yang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune System ◽  
Cord Blood ◽  
Genetic Model ◽  
Housekeeping Genes ◽  
Normal Pregnancy ◽  
Methylation Pattern ◽  
Whole Genome ◽  
Maternal Cell ◽  
Dna Methylation Pattern

The DNA methylation of human offspring can change due to the use of assisted reproductive technology (ART). In order to find the differentially methylated regions (DMRs) in ART newborns, cord blood maternal cell contamination and parent DNA methylation background, which will add noise to the real difference, must be removed. We analyzed newborns’ heel blood from six families to identify the DMRs between ART and natural pregnancy newborns, and the genetic model of methylation was explored, meanwhile we analyzed 32 samples of umbilical cord blood of infants born with ART and those of normal pregnancy to confirm which differences are consistent with cord blood data. The DNA methylation level was lower in ART-assisted offspring at the whole genome-wide level. Differentially methylated sites, DMRs, and cord blood differentially expressed genes were enriched in the important pathways of the immune system and nervous system, the genetic patterns of DNA methylation could be changed in the ART group. A total of three imprinted genes and 28 housekeeping genes which were involved in the nervous and immune systems were significant different between the two groups, six of them were detected both in heel blood and cord blood. We concluded that there is an ART-specific DNA methylation pattern involved in neuro- and immune-system pathways of human ART neonates, providing an epigenetic basis for the potential long-term health risks in ART-conceived neonates.

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