Newborn Umbilical Cord Blood DNA Methylation and Gene Expression Levels Exhibit Limited Association with Birth Weight

ABSTRACTBackgroundDNA methylation is highly sensitive to in utero perturbations and has an established role in both embryonic development and regulation of gene expression. The fetal genetic component has been previously shown to contribute significantly to the timing of birth, yet little is known about the identity and behavior of individual genes.ObjectivesThe aim of this study was to test the extent genome-wide DNA methylation levels in umbilical cord blood were associated with gestational age at birth (GA). Findings were validated in an independent sample and evidence for the regulation of gene expression was evaluated for cis gene relationships in matched specimens.ResultsGenome-wide DNA methylation, measured by the Illumina Infinium Human Methylation 450K BeadChip, was associated with GA for 2,372 CpG probes (5% false discovery rate) in both the Pregnancy, Race, Environment, Genes (PREG – Virginia Commonwealth University) and Newborn Epigenetic Study (NEST – Duke University) cohorts. Significant probes mapped to 1,640 characterized genes and an association with nearby gene expression measures obtained by the Affymetrix HG-133A microarray was found for 11 genes. Differentially methylated positions were enriched for actively transcribed and enhancer chromatin states, were predominately located outside of CpG islands, and mapped to genes enriched for inflammation and innate immunity ontologies. In both PREG and NEST, the first principal component derived from these probes explained approximately one-half (58.1% and 47.8%, respectively) of the variation in GA. This assessment provides a strong evidence to support the importance of DNAm change throughout the gestational time period.ConclusionsThese results converge on support for the role of variation in DNAm measures as an important genetic regulatory mechanism contributing to inter-individual differences in gestational age at birth. In particular, the pathways described are consistent with the well-known hypothesis of pathogen detection and response by the immune system to elicit premature labor as a consequence of unscheduled inflammation.

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A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

Genes ◽

10.3390/genes12060854 ◽

2021 ◽

Vol 12 (6) ◽

pp. 854

Author(s):

Yishu Wang ◽

Lingyun Xu ◽

Dongmei Ai

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Dna Methylation ◽

Regression Model ◽

The Cancer Genome Atlas ◽

Low Rank ◽

Expression Levels ◽

Rank Regression ◽

Prediction Of Prognosis ◽

Gene Expression Levels

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

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Associations between infant sex and DNA methylation across umbilical cord blood, artery, and placenta samples

Epigenetics ◽

10.1080/15592294.2021.1985300 ◽

2021 ◽

Author(s):

Anne K. Bozack ◽

Elena Colicino ◽

Allan C. Just ◽

Robert O. Wright ◽

Andrea A. Baccarelli ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Infant Sex

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Transcriptional Activity of Human Endogenous Retroviruses in Response to Prenatal Exposure of Maternal Cigarette Smoking

American Journal of Perinatology ◽

10.1055/s-0038-1675768 ◽

2018 ◽

Vol 36 (10) ◽

pp. 1060-1065 ◽

Cited By ~ 4

Author(s):

Massimiliano Bergallo ◽

Ilaria Galliano ◽

Valentina Daprà ◽

Alice Pirra ◽

Paola Montanari ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Tobacco Smoke ◽

Transcriptional Activity ◽

In Utero ◽

Endogenous Retroviruses ◽

Human Endogenous Retrovirus ◽

Human Umbilical Cord

Objective Transcription of human endogenous retrovirus (HERV) elements is usually suppressed by epigenetic factors such as DNA methylation and heterochromatin silencing by histone modifications. There is an association between maternal smoking during pregnancy and DNA methylation levels in placental tissue and in DNA from cord blood. Study Design We assessed the transcriptional activity of HERV-H, HERV-K, and HERV-W in umbilical cord blood from 47 term babies unexposed to tobacco smoke in utero and 23 term babies exposed to tobacco smoke in utero. Results In our population, the HERV-H, HERV-K, and HERV-W families were always transcriptionally active, and the levels of all HERVs (H, K, W) were significantly higher in unexposed than smoke-exposed babies. Conclusion This study provides preliminary information about the transcriptional activity of HERV-H, HERV-K, and HERV-W families in human umbilical cord blood.

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Antenatal depression, infants’ neurobehavioral development and global dNA methylation in placenta and umbilical-cord blood

Comprehensive Psychiatry ◽

10.1016/j.comppsych.2012.07.036 ◽

2013 ◽

Vol 54 (1) ◽

pp. e7

Author(s):

E. Mystal ◽

A. Rialdi ◽

Y. Ma ◽

L. Lambertini ◽

J. Chen ◽

...

Keyword(s):

Dna Methylation ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Antenatal Depression ◽

Global Dna Methylation ◽

Neurobehavioral Development

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Umbilical Cord Blood DNA Methylation in Children Who Later Develop Type 1 Diabetes

10.1101/2021.05.21.21257593 ◽

2021 ◽

Author(s):

Essi Laajala ◽

Ubaid Ullah ◽

Toni Grönroos ◽

Omid Rasool ◽

Viivi Halla-aho ◽

...

Keyword(s):

Dna Methylation ◽

Type 1 Diabetes ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Reduced Representation ◽

Prediction And Prevention ◽

Develop Type ◽

Methylation Patterns

Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine, whether perinatal DNA methylation could be associated with later progression to type 1 diabetes. Reduced representation bisulfite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Type 1 Diabetes Prediction and Prevention (DIPP) study. Children later diagnosed with type 1 diabetes and/or testing positive for multiple islet autoantibodies (N=43) were compared to control individuals (N=79), who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis. No differences in the cord blood methylation patterns were observed between these cases and controls.

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Immunoglobulin gene expression in umbilical cord blood-derived CD34+ hematopoietic stem/progenitor cells

Gene ◽

10.1016/j.gene.2015.08.046 ◽

2016 ◽

Vol 575 (1) ◽

pp. 108-117 ◽

Cited By ~ 1

Author(s):

Jingfang Liu ◽

Miaoran Xia ◽

Pingzhang Wang ◽

Chong Wang ◽

Zihan Geng ◽

...

Keyword(s):

Gene Expression ◽

Cord Blood ◽

Progenitor Cells ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Immunoglobulin Gene ◽

Hematopoietic Stem

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Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Human Molecular Genetics ◽

10.1093/hmg/ddz067 ◽

2019 ◽

Vol 28 (15) ◽

pp. 2477-2485 ◽

Cited By ~ 1

Author(s):

Diana A van der Plaat ◽

Judith M Vonk ◽

Natalie Terzikhan ◽

Kim de Jong ◽

Maaike de Vries ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Occupational Exposure ◽

Health Effects ◽

Mineral Dust ◽

Occupational Exposures ◽

Expression Levels ◽

Adverse Health Effects ◽

Never Smokers ◽

Gene Expression Levels

Abstract Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were associated with gases/fumes and 7 with mineral dust. Three of these DMRs were associated with both exposures (RPLP1 and LINC02169 (2×)) and 11 DMRs were located within transcript start sites of gene expression regulating genes. We replicated two DMRs with gases/fumes (VTRNA2-1 and GNAS) and one with mineral dust (CCDC144NL). In addition, nine gases/fumes DMRs and six mineral dust DMRs significantly associated with gene expression levels. Our data suggest that occupational exposures may induce differential methylation of gene expression regulating genes and thereby may induce adverse health effects. Given the millions of workers that are exposed daily to occupational exposures, further studies on this epigenetic mechanism and health outcomes are warranted.

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Associations between piglet umbilical blood hematological criteria, birth order, birth interval, colostrum intake, and piglet survival

Journal of Animal Science ◽

10.1093/jas/skaa329 ◽

2020 ◽

Vol 98 (10) ◽

Author(s):

Kiah M Gourley ◽

Joel M DeRouchey ◽

Mike D Tokach ◽

Steve S Dritz ◽

Robert D Goodband ◽

...

Keyword(s):

Carbon Dioxide ◽

Birth Weight ◽

Cord Blood ◽

Birth Order ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Birth Interval ◽

Blood Ph ◽

Umbilical Cords ◽

Piglet Survival

Abstract A total of 656 pigs (623 live-born and 33 stillborn) from 43 sows were used to evaluate hematological criteria at birth and their association with piglet survival. At birth of each piglet, birth time and order within the litter, weight, umbilical cord status (intact or ruptured) and whether the pig was live-born or stillborn were recorded. A 200µL sample of blood from the umbilical cord was collected and immediately analyzed for concentrations of glucose, oxygen partial pressure (pO2), carbon dioxide partial pressure (pCO2), pH, base excess (BE), bicarbonate (HCO3), saturated oxygen (sO2), total carbon dioxide (TCO2), sodium, potassium, ionized calcium (iCa), hematocrit (Hct), and hemoglobin (Hb) on a hand held iStat portable clinical analyzer (iStat Alinity, Abbott Point of Care Inc., Princeton, NJ). Piglets were categorized into quartiles based on birth order and cumulative birth interval (CumBI). Live-born pigs had higher (P < 0.01) umbilical cord blood pH, HCO3, BE, sO2, TCO2, and birth weight compared with stillborn pigs, but lower (P < 0.01) pCO2, K, iCa, and glucose compared with stillborn pigs. Pigs with intact umbilical cords at birth were associated with higher (P < 0.01) blood pH, HCO3, BE, and TCO2 compared with piglets born with a ruptured umbilical cord. Pigs with intact umbilical cords were associated with lower (P < 0.01) Hct and Hb concentrations and born earlier (P < 0.01) in the birth order compared with pigs born with a ruptured umbilical cord. Pigs that did not survive to weaning had lower (P < 0.01) umbilical cord blood pH, HCO3, BE, sO2, TCO2, Na, glucose, and birth weight, and 24 hr weight compared with pigs alive at weaning. Pigs born in the first quartile for CumBI had higher (P <0.05) pH compared with pigs in the other three quartiles. Umbilical cord blood HCO3, BE, and TCO2 decreased (P <0.05) with each change in CumBI quartile from first to last. Blood glucose was lowest (P <0.05) in pigs born before 44 min and highest in pigs born after 164 min. Umbilical cord blood pH, HCO3, BE, TCO2, Na, glucose, Hct, and Hb were positively associated (P <0.001) with colostrum intake, indicating increased blood values resulted in higher colostrum intake. Although a pig may be live-born, their survival to 24 hr and to weaning is reduced when blood pH, HCO3, BE, and sO2 are lower reiterating the importance of management practices that can reduce the birth interval between pigs and the number of pigs experiencing moderate to severe hypoxia.

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