Methylation status of
            <i>VTRNA2-1</i>
            /
            <i>nc886</i>
            is stable across populations, monozygotic twin pairs and in majority of tissues

Marttila, Saara; Tamminen, Hely; Rajić, Sonja; Mishra, Pashupati P.; Lehtimäki, Terho; Raitakari, Olli T.; Kähönen, Mika; Kananen, Laura; Jylhävä, Juulia; Hägg, Sara; Delerue, Thomas; Peters, Annette; Waldenberger, Mélanie; Kleber, Marcus E.; März, Winfried; Luoto, Riitta; Raitanen, Jani; Sillanpää, Elina; Laakkonen, Eija K.; Heikkinen, Aino; Ollikainen, Miina; Raitoharju, Emma

doi:10.2217/epi-2022-0228

Cited by 6 publications

(3 citation statements)

References 115 publications

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“…S4). Human studies have shown that methylation at CoRSIVs is stable for years in the same individual [ 12 , 22 , 23 ]. It is possible, therefore, that profiling CoRSIV methylation in peripheral blood DNA of calves could someday be utilized to identify those individuals most likely to exhibit traits favorably associated with productivity in adulthood.…”

Section: Discussionmentioning

confidence: 99%

Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans

Chang,

Baker,

Laritsky

et al. 2024

Genome Biol

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Background We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle. Results Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, our approach identifies 217 cattle CoRSIVs, a subset of which we independently validate by bisulfite pyrosequencing. Similar to human CoRSIVs, those in cattle are strongly associated with genetic variation. Also as in humans, we show that establishment of DNA methylation at cattle CoRSIVs is particularly sensitive to early embryonic environment, in the context of embryo culture during assisted reproduction. Conclusions Our data indicate that CoRSIVs exist in cattle, as in humans, suggesting these systemic epigenetic variants may be common to mammals in general. To the extent that individual epigenetic variation at cattle CoRSIVs affects phenotypic outcomes, assessment of CoRSIV methylation at birth may become an important tool for optimizing agriculturally important traits. Moreover, adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes by engineering CoRSIV methylation profiles.

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Section: Discussionmentioning

confidence: 99%

Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans

Chang,

Baker,

Laritsky

et al. 2024

Genome Biol

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“…We therefore performed DNAmethylation profiling on biopsies taken from all genotypes and animals at 10 days of age (i.e., before weaning). We used ear clips as they are minimally invasive for young mice and are similar to tissues used to identify early-life epigenetic signatures in humans [50][51][52][53][54][55] . We used Illumina Infinium Mouse Methylation BeadChips to quantify DNA methylation state at ~285,000 CpG sites that included CpGs in all annotated genes, functional RNAs, and cis-regulatory regions of the mouse genome.…”

Section: Trim28-dependent Developmental Heterogeneity Primes Cancer O...mentioning

confidence: 99%

Developmental priming of cancer susceptibility

Panzeri,

Fagnocchi,

Apostle

et al. 2023

Preprint

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DNA mutations are necessary drivers of cancer, yet only a small subset of mutated cells go on to cause the disease. To date, the mechanisms that determine which rare subset of cells transform and initiate tumorigenesis remain unclear. Here, we take advantage of a unique model of intrinsic developmental heterogeneity (Trim28+/D9) and demonstrate that stochastic early life epigenetic variation can trigger distinct cancer-susceptibility ′states′ in adulthood. We show that these developmentally primed states are characterized by differential methylation patterns at typically silenced heterochromatin, and that these epigenetic signatures are detectable as early as 10 days of age. The differentially methylated loci are enriched for genes with known oncogenic potential. These same genes are frequently mutated in human cancers, and their dysregulation correlates with poor prognosis. These results provide proof-of-concept that intrinsic developmental heterogeneity can prime individual, life-long cancer risk.

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“…Aberrantly methylated iDMRs were defined as iDMRs showing differentially methylated levels in at least two consecutive probes within iDMRs which included at least four significant probes [19]. The VTRNA2-1:DMR was considered as insignificant because it has been shown to be polymorphically imprinted in general population, showing frequent hypomethylation with various degrees [29]. We considered each patient as having MLID if showing aberrant methylation in one or more additional iDMRs other than the disease-related iDMRs.…”

Section: Gwma and Data Analysismentioning

confidence: 99%

Uncovering the phenotypic consequences of multi-locus imprinting disturbances using genome-wide methylation analysis in genomic imprinting disorders

Kim,

Shin,

Shin

et al. 2023

PLoS ONE

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Imprinted genes are regulated by DNA methylation of imprinted differentially methylated regions (iDMRs). An increasing number of patients with congenital imprinting disorders (IDs) exhibit aberrant methylation at multiple imprinted loci, multi-locus imprinting disturbance (MLID). We examined MLID and its possible impact on clinical features in patients with IDs. Genome-wide DNA methylation analysis (GWMA) using blood leukocyte DNA was performed on 13 patients with Beckwith–Wiedemann syndrome (BWS), two patients with Silver–Russell syndrome (SRS), and four controls. HumanMethylation850 BeadChip analysis for 77 iDMRs (809 CpG sites) identified three patients with BWS and one patient with SRS showing additional hypomethylation, other than the disease-related iDMRs, suggestive of MLID. Two regions were aberrantly methylated in at least two patients with BWS showing MLID: PPIEL locus (chromosome 1: 39559298 to 39559744), and FAM50B locus (chromosome 6: 3849096 to 3849469). All patients with BWS- and SRS-MLID did not show any other clinical characteristics associated with additional involved iDMRs. Exome analysis in three patients with BWS who exhibited multiple hypomethylation did not identify any causative variant related to MLID. This study indicates that a genome-wide approach can unravel MLID in patients with an apparently isolated ID. Patients with MLID showed only clinical features related to the original IDs. Long-term follow-up studies in larger cohorts are warranted to evaluate any possible phenotypic consequences of other disturbed imprinted loci.

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Methylation status of VTRNA2-1 / nc886 is stable across populations, monozygotic twin pairs and in majority of tissues

Cited by 6 publications

References 115 publications

Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans

Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans

Developmental priming of cancer susceptibility

Uncovering the phenotypic consequences of multi-locus imprinting disturbances using genome-wide methylation analysis in genomic imprinting disorders

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