• Three factors have been suggested to increase phenotypic variability and thus potentially the resilience of tree populations: intraspecific genetic variability, (micro-)environmental variation, and epigenetic variation. (uni-marburg.de)
  • The application of selection pressure led to a reduction in genetic polymorphism and an increase of bulb weight, but did not influence epigenetic polymorphism, indicating that it is independent of genetic variability. (conicet.gov.ar)
  • It's becoming evident that both genetic variability and epigenetic mechanisms are built into the genome as adaptive systems of variation that allow for robust speciation to occur within the boundaries of created kinds. (icr.org)
  • METHODS: Herein, we used Nanopore sequencing to investigate SVA genetic variability and methylation. (uni-luebeck.de)
  • Within the SVA locus, there was no difference in genetic variability other than variations of the repeat motif between patients. (uni-luebeck.de)
  • It is caused by a SINE-VNTR-Alu (SVA) retrotransposon insertion in the TAF1 gene with a polymorphic (CCCTCT)n domain that acts as a genetic modifier of disease onset and expressivity.METHODS: Herein, we used Nanopore sequencing to investigate SVA genetic variability and methylation. (uni-luebeck.de)
  • Phenotypic variability shown in in vitro culture systems is due to high genotype dependence, going from species level to the level of cultivar/variety and individual genotypes. (frontiersin.org)
  • Furthermore, phenotypic changes induced by epigenetic variation can be inherited across several generations (especially across clonal generations), suggesting that variation in DNA methylation might contribute to heritable phenotypic variation and, eventually, to adaptation. (uni-marburg.de)
  • An exhaustive search for pairwise phenotypic correlations between gene expression and DNA methylation in samples from human blood ( n = 610) was performed. (biomedcentral.com)
  • iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. (ca.gov)
  • Between 15 and 18% of genes with DNA methylation changes were differentially expressed in CD4 + T cells in vivo. (biomedcentral.com)
  • In this study, we performed quantitative methylation analyses of six differentially methylated imprinted genes (H19, MEG3, LIT1, NESP55, PEG3 and SNRPN), one hypermethylated pluripotency gene (OCT4) and one hypomethylated tumor suppressor gene (APC) in chorionic villus, fetal and adult cortex, and adult blood samples. (uni-wuerzburg.de)
  • However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. (ca.gov)
  • Somatic DNA methylation patterns that can persist throughout life are established shortly after fertilisation when the majority of epigenetic marks, including DNA methylation, are erased from the pre-implantation embryo. (frontiersin.org)
  • Placenta-associated pregnancy complications, such as preeclampsia and intrauterine growth restriction, are all associated with aberrant patterns of DNA methylation and expression which are only now being linked to disease risk later in life. (frontiersin.org)
  • Part of this connection may come through DNA methylation, patterns of which are known to change under different conditions. (frontiersin.org)
  • Thus, we aim to test the influence of DNA methylation changes on the in vitro differentiation process of HD-hiPS toward post-mitotic medium sized spiny neurons, in order to check for potential modifications in the methylation patterns. (bmj.com)
  • Just one year prior to this 2014 study, 1 the epigenetic basis of speciation was demonstrated in birds in which the progressive geographical spread and ecological patterns of adaptation for a newly introduced songbird species were characterized by differences in DNA methylation patterns, not variation in the actual DNA sequence. (icr.org)
  • The second factor studied was epigenetically-based, using an analysis of DNA methylation patterns around the genome. (icr.org)
  • 2013. Patterns of DNA methylation throughout a range expansion of an introduced songbird. (icr.org)
  • In order to mitigate spurious associations in such association studies, it is crucial to elucidate and account for the sources of variation that globally affect the methylation patterns in the genome. (biomedcentral.com)
  • The association of aberrant sperm DNA methylation patterns and compromised semen parameters suggests that disturbances in male germline epigenetic reprogramming contribute to this problem. (uni-wuerzburg.de)
  • However, little is known about the natural variation of genespecific methylation patterns. (uni-wuerzburg.de)
  • We found considerable variability of functionally important methylation patterns among unrelated healthy individuals and a trend toward more similar methylation levels in monozygotic twins than in dizygotic twins. (uni-wuerzburg.de)
  • The past decade has witnessed an exponential increase in epidemiologic studies of DNA methylation, driven in large part by increasing appreciation for its critical role in the development and progression of human diseases together with the declining cost of high-throughput technologies for interrogating the epigenome. (biomedcentral.com)
  • Numerous studies of DNA methylation from buccal and saliva have shown a relatively large amount of variation compared to other tissues. (epigenie.com)
  • Variation in DNA methylation can be under genetic control, arise stochastically, or be induced by environmental conditions. (uni-marburg.de)
  • In simulation studies, adjustments for cell composition using the IDOL library resulted in uniformly lower false positive rates compared to competing libraries, while also demonstrating an improved capacity to explain epigenome-wide variation in DNA methylation within two large publicly available HM450 data sets. (biomedcentral.com)
  • Following the namesake adopted for genome-wide, genetic association studies of disease phenotypes (GWAS), studies investigating the role of DNA methylation in human diseases and exposures have been aptly dubbed epigenome-wide association studies (EWAS) [ 1 ]. (biomedcentral.com)
  • Pregnancy exposure to phthalates and DNA methylation in male placenta - An epigenome-wide association study. (cdc.gov)
  • iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. (ca.gov)
  • Retrospective studies of the survivors of famines, such as those exposed to the Dutch Hunger Winter of 1944-45, have linked exposures around conception to later disease outcomes, some of which correlate with DNA methylation changes at certain genes. (frontiersin.org)
  • Here, effects of changes in methylation status of 5-methyl cytosine in melatonin and female hormone receptor genes were investigated as possible mechanisms for increased breast cancer risk in female night shift workers. (fortunejournals.com)
  • Methylation in promoter regions of the MTNR1A, MTNR1B, PGR, ESR1 and ESR2 genes was analyzed by pyrosequencing in a nested case-control study of female nurses, including 354 breast cancer cases and 356 healthy controls. (fortunejournals.com)
  • No association between promoter methylation levels and breast cancer risk was observed for the other receptor genes investigated. (fortunejournals.com)
  • In contrast, nonpathogenic SIVagm infection induced DNA methylation in genes coding for regulatory proteins such as LAG-3, arginase-2, interleukin-21 and interleukin-31. (biomedcentral.com)
  • Although more highly transcribed genes acquire methylation earlier, the major transitions in the oocyte transcriptome occur well before the de novo methylation phase, indicating that transcription is generally not rate limiting in conferring permissiveness to DNA methylation. (biomedcentral.com)
  • Epigenetic modifications, such as DNA methylation, have an important role in controlling when and where genes are expressed, and can be influenced by environmental factors. (biomedcentral.com)
  • In 2009, Yehuda and Bierer posited that epigenetic modifications, such as DNA methylation, may occur in response to environmental influences such as trauma exposure, thus altering the functional expression of genes. (cdc.gov)
  • The main mechanisms of epigenetic alterations are DNA methylation, histone modifications, and regulation by non-coding RNAs. (wikipedia.org)
  • This study also confirmed that age-related DNA methylation is associated to a certain extent with transcriptional modifications. (pasteur.fr)
  • Multiple mechanisms have evolved to perform these essential functions: DNA methylation, a bewildering array of histone modifications, RNA-based regulation, etc. (aacrjournals.org)
  • Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. (bcu.ac.uk)
  • Therefore, the period around conception is potentially critical for influencing DNA methylation, including methylation at imprinted alleles and metastable epialleles (MEs), loci where methylation varies between individuals but is correlated across tissues. (frontiersin.org)
  • We detected changes in the amount of each methylation pattern (unmethylated, hemimethylated and internally methylated) among the different years analyzed while 82.47 and 19.61% of the genetic and epigenetical loci were stable during the time of culture. (conicet.gov.ar)
  • Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. (bcu.ac.uk)
  • We assessed the sex-specific association between residential PM 2.5 exposure during pregnancy and the methylation level of CpG loci mapping to the IGF2 / H19 cluster, and identified prenatal vulnerability by investigating susceptible time windows of exposure. (biomedcentral.com)
  • Variants were frequently familial, and genotype-phenotype analyses demonstrated striking interfamilial and intrafamilial variability. (springer.com)
  • The aims of the present study were to develop a robust internal control for ddPCR DNA methylation analyses and demonstrate its value in terms of increased precision of the normalized methylation data. (biomedcentral.com)
  • Recently, the placenta, a tissue with a unique hypomethylated methylome, has been shown to possess great inter-individual variability, which we highlight as a promising target tissue for studying MEs and mixed environmental exposures. (frontiersin.org)
  • All omics displayed a large range of intra- and inter-individual variability depending on each omics feature, although all presented a highest median intra-individual variability. (biomedcentral.com)
  • In this paper, we define "intra-individual variability" as the variability estimated within individuals over time and "inter-individual variability" as the between-individuals variability. (biomedcentral.com)
  • While GWAS and EWAS data share many of the same analytical challenges, the tissue specificity of DNA methylation presents an added layer of complexity in the analysis, and particularly in the interpretation of EWAS. (biomedcentral.com)
  • Results Global CpG methylation showed statistical significant differences in the methylation percentages of HD-iPS compared to control-iPS during the differentiation process. (bmj.com)
  • Although such studies may be less prone to confounding by leukocyte-lineage heterogeneity compared to those involving whole blood (WB) DNA methylation assessments, purification of cell populations carrying these markers will not completely eliminate heterogeneity attributable to lineage differences [ 3 ]. (biomedcentral.com)
  • The use of the 4Plex for normalization reduced the variability in methylation values, corrected for differences in template amount, and diminished the effect of chromosomal aberrations. (biomedcentral.com)
  • However, methylation of CpG islands (CGIs) is delayed compared with the genome average and there are reproducible differences amongst CGIs in onset of methylation. (biomedcentral.com)
  • Limiting dilution bisulfite sequencing of small pools of sperm from fertile donors did not reveal significant differences in the occurrence of abnormal methylation imprints between sperm with and without morphological abnormalities. (uni-wuerzburg.de)
  • The relative differences in methylation among neighboring CpGs in the generally hypomethylated APC promoter may not only reflect stochastic fluctuations but also depend on the tissue type. (uni-wuerzburg.de)
  • It should be noted that epigenetic clocks based on DNA methylation are constructed from data from multiple tissues from a mixture of different cell types. (pasteur.fr)
  • DNA methylation is the most commonly studied epigenetic mark in humans, as it is well recognised as a stable, heritable mark that can affect genome function and influence gene expression. (frontiersin.org)
  • Animal models have shown more directly that DNA methylation can be affected by dietary supplements that act as cofactors in one-carbon metabolism, and in humans, methylation at birth has been associated with peri-conceptional micronutrient supplementation. (frontiersin.org)
  • Commentary on: Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age. (aging-us.com)
  • Whereas DNA methylation has been long associated with epigenetic inheritance, recent work clearly demonstrates that genetic factors explain a substantial proportion of the variability of DNA methylation in humans, with the average narrow sense heritability being approximately 0.2 [ 2 ]. (biomedcentral.com)
  • MRLs include adjustments to reflect human variability from laboratory animal data to humans. (cdc.gov)
  • We show through simulations and real data that our method, CONFINED, is not only more accurate than the state-of-the-art reference-free methods for capturing known, replicable biological variability, but it is also considerably more robust to dataset-specific technical variability than previous approaches. (biomedcentral.com)
  • The epigenetic potential of DNA methylation inhibitors may be limited by other epigenetic mechanisms that are also worth exploring as therapeutic targets. (aacrjournals.org)
  • therefore, it provides a unique opportunity to investigate the extent to which different sequence features acquire methylation as a result of common or distinct mechanisms. (biomedcentral.com)
  • A reduction in the number of cells, the change in structure and functioning of organs, permanent change in DNA methylation, and in gene expression have also been considered to be molecular mechanisms responsible for fetal programming 1 . (bvsalud.org)
  • CONCLUSIONS: Nanopore sequencing can reliably detect SVA hexanucleotide repeat numbers, methylation and, lastly, variation in the repeat motif. (uni-luebeck.de)
  • Statistical methods leveraging the tissue-specificity of DNA methylation for deconvoluting the cellular mixture of heterogenous biospecimens offer a promising solution, however the performance of such methods depends entirely on the library of methylation markers being used for deconvolution. (biomedcentral.com)
  • Given how common low-quality buccal samples appear to be, and the large amount of variability within them, correction methods such as this one may become a standard processing step in DNA methylation studies moving forward. (epigenie.com)
  • Reference-based methods and methods that leverage prior statistics, however, are limited to known sources of variability for which such reference data exists. (biomedcentral.com)
  • Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner. (bcu.ac.uk)
  • Both average methylation level and range of methylation variation depended on the gene locus, tissue type and/or developmental stage. (uni-wuerzburg.de)
  • Our results are consistent with the view that most methylation variation may arise after fertilization, leading to epigenetic mosaicism. (uni-wuerzburg.de)
  • Blood cell DNA methylation biomarkers in preclinical malignant pleural mesothelioma: The EPIC prospective cohort. (who.int)
  • DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. (springer.com)
  • Functionality of the DNA methylation was annotated by the association to fetal growth and cellular pathways. (biomedcentral.com)
  • Alterations in methylation of the imprinted IGF2/H19 cluster might be a potential mechanism underlying the association between in utero PM 2.5 exposure and fetal growth, as maternal residential PM 2.5 has been reported to alter their expression [ 22 ]. (biomedcentral.com)
  • These results do not support a major role for transcriptional transitions in the time of onset of DNA methylation in the oocyte, but suggest a model in which sequences least dependent on chromatin remodelling are the earliest to become permissive for methylation. (biomedcentral.com)
  • This variability in response, known as in vitro recalcitrance, could be described as varying capacity for plant cells to adapt to new environmental conditions, i.e., the capacity to develop and express new cell programs. (frontiersin.org)
  • The laboratories of Michael Brudno and Rosanna Weksberg at the Hospital for Sick Children (Toronto, Canada) sought to identify and correct for blood cell contamination in buccal/saliva sample DNA methylation data. (epigenie.com)
  • Using six blood cell types and purified buccal cell DNA methylation data as a reference, they estimated cell-type composition for 11 published DNA methylation studies that used the 450k array. (epigenie.com)
  • We determined that the correlation structure between probe pairs was largely due to blood cell type specificity of the expression and methylation probes. (biomedcentral.com)
  • To the best of our knowledge, this is the first study investigating the association between prenatal PM 2.5 exposure and newborn DNA methylation of the IGF2/H19 . (biomedcentral.com)
  • The results of our study provided evidence that prenatal PM 2.5 exposure is associated with DNA methylation in newborns' IGF2/H19 . (biomedcentral.com)
  • Methylation datasets are affected by innumerable sources of variability, both biological (cell-type composition, genetics) and technical (batch effects). (biomedcentral.com)
  • In the case of methylation, one commonly researched source of biological variability is cell-type composition. (biomedcentral.com)
  • We found that individual CpGs had low variance and that variability was suppressed in promoters. (bcu.ac.uk)
  • We noted that DNA methylation variation was highly heritable (h(2)median = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. (bcu.ac.uk)
  • Background The variability of Huntington's disease phenotype could be mostly explained through the number of CAG repeats in HTT gene. (bmj.com)
  • Further studies will allow to elucidate the real contribution of DNA methylation in HD pathogenesis and phenotype. (bmj.com)
  • Finally, we discussed the implications of the high epigenetic variability of an agamic propagated species and its possible effect on the phenotype. (conicet.gov.ar)
  • This review will summarise current knowledge on the effect of early environmental exposure on later disease risk, especially where this may be mediated by DNA methylation. (frontiersin.org)
  • Inter-individual epigenetic variance may also have a significant role in the observed biomarker variability following isocyanate exposure. (cdc.gov)
  • We investigated the association between cord blood DNA methylation status of the IGF2/H19 gene cluster and maternal fine particulate matter exposure during fetal life. (biomedcentral.com)
  • In this study, we assessed the association between maternal PM 2.5 exposure during pregnancy and the DNA methylation level specific to IGF2/H19 gene cluster in cord blood collected at birth. (biomedcentral.com)
  • Upon adjustment of the expression and methylation values for observed blood cellular composition ( n = 422), the number of probe pairs which survived Bonferroni correction reduced by more than 5400 fold. (biomedcentral.com)
  • DNA methylation is an epigenetic modification that interferes with transcription and causes decreased levels of gene expression. (wikipedia.org)
  • DNA methylation is an epigenetic modification that plays an important role in gene regulation. (uni-wuerzburg.de)
  • PacBio modification analysis revealed that 1 of these sites might have been modified ( Appendix Figure 1, panel B). Bst EII is sensitive to methylation and other types of DNA modification ( 14 ). (cdc.gov)
  • Application of IDOL to training set consisting of samples with both whole-blood DNA methylation data (Illumina HumanMethylation450 BeadArray (HM450)) and flow cytometry measurements of cell composition revealed an optimized library comprised of 300 CpG sites. (biomedcentral.com)
  • A total of 610 individuals from the BSGS data set had both gene expression and DNA methylation measures as well as high density genotypes [ 14 ]. (biomedcentral.com)
  • The sample included 842 respondents in MESA with DNA methylation data collected between 2010-2012 who answered questions on early life adversities in a 2018-2019 phone follow-up. (cdc.gov)
  • Given the predominant role of transcription, we sought to investigate whether transcription timing is rate limiting for de novo methylation and determines the asynchrony of methylation events. (biomedcentral.com)
  • Finally, mediation analysis was performed to investigate whether DNA methylation of cg21325723 mediates this gene-environment interaction on the risk of developing of ACPA-positive RA. (biomedcentral.com)
  • This study was undertaken to evaluate whether DNA methylation can mediate the interaction between genotype and smoking in the development of anti-citrullinated peptide antibody (ACPA)-positive RA. (biomedcentral.com)
  • In studies attempting to determine the molecular basis for beak variability in finches, researchers have found that very similar developmental genetic pathways among species can produce markedly different beak shapes. (icr.org)
  • We further performed a multi-omics network analysis to establish clusters of co-varying omics features and assessed the contribution of key variables (including biological traits and sample collection parameters) to omics variability. (biomedcentral.com)
  • For increased precision of the methylation analysis, we aimed to develop a robust internal control for use in methylation-specific ddPCR. (biomedcentral.com)
  • Implementation of a robust internal control, i.e., the 4Plex, and an algorithm for automated threshold determination, PoDCall, in methylation-specific ddPCR increase the precision of DNA methylation analysis. (biomedcentral.com)
  • Here, we propose a reference-free method based on sparse canonical correlation analysis to separate the biological from technical sources of variability. (biomedcentral.com)
  • To detect methylation from blood- and brain-derived DNA, we used a Cas9-targeted approach.RESULTS: High concordance was observed for hexanucleotide repeat numbers detected with Nanopore sequencing and fragment analysis. (uni-luebeck.de)
  • Many of the protein pathway functions overlap with previous findings on genetic markers associated with variability both in isocyanate biomarker levels and asthma susceptibility, which suggests there are overlapping protein pathways that contribute to both isocyanate toxicokinetics and toxicodynamics. (cdc.gov)
  • Furthermore, MTNR1A methylation levels were not affected by shift work. (fortunejournals.com)
  • In vertebrates, gene expression is modulated in particular by methylation within a region of the genome known as a CpG island, a region near a gene's promoter that contains a high percentage of cytosine and guanine nucleotides. (wikipedia.org)
  • We demonstrate that increased methylation of the MTNR1A promoter is associated with increased risk of breast cancer (OR=1.13, 95% CI: 1.02 -1.24, P=0.019). (fortunejournals.com)