The effect of genotype and in utero environment on inter-individual variation in neonate DNA methylomes
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Joanna Holbrook
PROVIDER: E-GEOD-54446 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. Although methQTLs were readily detected in neonatal methylomes, genotype alone did not explain the majority of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age and birth order. We surveyed the genotypes and DNA methylomes of 237 neonates and included 32 technical replicates
2014-04-02 | E-GEOD-53816 | biostudies-arrayexpress
Project description:We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. Although methQTLs were readily detected in neonatal methylomes, genotype alone did not explain the majority of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age and birth order. We surveyed the genotypes and DNA methylomes of 237 neonates
2014-04-02 | E-GEOD-54445 | biostudies-arrayexpress
Project description:Background: Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth. Methods: Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood (for methylation arrays) and maternal peripheral venous blood (for cotine level measurement) were collected and an epigenome-wide association study was performed using a 450K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood. Results: The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (FisherM-bM-^@M-^Ys exact test, p=0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene. Conclusions: In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease. Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood were collected and an epigenome-wide association study was performed using a 450K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood.
2015-02-16 | E-GEOD-64316 | biostudies-arrayexpress
Project description:We performed a proteomic profiling of human mesenchymal stem cells (hMSCs) derived from adipose tissue or umbilical cord.
2018-07-11 | PXD009893 | Pride
Project description:There is extensive variation in DNA methylation between individuals and ethnic groups. These differences can arise from a combination of genetic and non-genetic influences and potential modifiers include nutritional cues, early life experience, and social and physical environments. Here we have assayed genome-wide DNA methylation in neonatal cord blood from African American, European American, and other ancestral groups. This is part of the CANDLE Study (Conditions Affecting Neurocognitive Development and Learning in Early Childhood). Our overarching goal is to determine the different environmental and maternal factors that can modify DNA methylation in newborns. This is a cross-sectional study of a total of 216 racially diverse participants of CANDLE. Cordblood was collected at birth. DNA methylation was measured using the Illumina HumanMethylation27 BeadChip. Based on maternal self-report, the samples are 112 African Americans, 91 European Americans and 13 other racial or mixed race group.
2015-01-14 | E-GEOD-64940 | biostudies-arrayexpress
Project description:Background: Changes in DNA methylation patterns with age frequently have been observed and implicated in the normal aging process and its associated increasing risk of disease, particularly cancer. Additionally, the offspring of older parents are at significantly increased risk of cancer, diabetes, and neurodevelopmental disorders. Only a proportion of these increased risks among the children of older parents can be attributed to nondisjunction and chromosomal rearrangements. Results: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels. Conclusions: These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life. 168 newborn umbilical cord buffy coat samples run singly as a cross-sectional study, not case-control.
2011-08-31 | E-GEOD-27317 | biostudies-arrayexpress
Project description:Analysis of umbilical cord tissue in newborns of type 1 diabetic mothers at gene expression level. The hypothesis tested in the present study was that intrauterine diabetic milieu may effect of fetal umbilical cord gene expression, and via umbilical cord, the alterations may be produced in other fetal tissues as well. Results provide an information of the differentially expressed genes and enriched pathways, such as the dowregulated genes on the pathway on blood vessel development in umbilical cords from diabetic pregnancies. Umbilical cord tissue was collected after elective ceasarean section and was immediately flash frozen in liquid nitrogen and stored at -80C until total RNA extraction from the whole tissue sample. Six cords exposed to maternal diabetes (DM) and six control cords (C) from healthy pregnancies were analyzed.
2016-07-03 | E-GEOD-51546 | biostudies-arrayexpress
Project description:Transcription profiling of human umbilical cord blood derived Outgrowth Endothelial Cells (OECs) at early and late passages. Outgrowth endothelial cells were isolated from the mononuclear fraction of umbilical cord blood and cultured on collagen coated flasks. Once OEC colonies emerged they were expanded in culture to study cell growth kinetics. Total RNA was extracted from OECs at an early passage and OECs at a late passage which were becoming senescent . The purpose of this experiment was to were compared early and late passage OECs to determine how senescence affects the gene expression profile of OECs.
2013-03-16 | E-MTAB-1388 | biostudies-arrayexpress
Project description:Background: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. Methods: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina® Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. Results: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. Conclusions: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention. Longitudinal study including 15 samples
2016-06-15 | E-GEOD-83334 | biostudies-arrayexpress
Project description:Receptor tyrosine kinase (RTK)-dependent signaling has been implicated in the pathogenesis of acute lymphoblastic leukemia (ALL) of childhood. However, the RTK-dependent signaling state and its interpretation with regard to biological behavior are often elusive. To decipher signaling circuits that link RTK activity with biological output in vivo, we established patient-derived xenograft ALL (PDX-ALL) models with dependencies on fms-like tyrosine kinase 3 (FLT3) and platelet-derived growth factor receptor β (PDGFRB), which were interrogated by phosphoproteomics using iTRAQ mass spectrometry. Signaling circuits were determined by receptor type and cellular context with few generic features, among which we identified group I p21-activated kinases (PAKs) as potential therapeutic targets. Growth factor stimulation markedly increased catalytic activities of PAK1 and PAK2. RNA interference (RNAi)-mediated or pharmacological inhibition of PAKs using allosteric or adenosine triphosphate (ATP)-competitive compounds attenuated cell growth and increased apoptosis in vitro. Notably, PAK1- or PAK2-directed RNAi enhanced the antiproliferative effects of the type III RTK and protein kinase C inhibitor midostaurin. Treatment of FLT3- or PDGFRB-dependent ALLs with ATP-competitive PAK inhibitors markedly decreased catalytic activities of both PAK isoforms. In FLT3-driven ALL, this effect was augmented by coadministration of midostaurin resulting in synergistic effects on growth inhibition and apoptosis. Finally, combined treatment of FLT3 D835H PDX-ALL with the ATP-competitive group I PAK inhibitor FRAX486 and midostaurin in vivo significantly prolonged leukemia progression-free survival compared with midostaurin monotherapy or control. Our study establishes PAKs as potential downstream targets in RTK-dependent ALL of childhood, the inhibition of which might help prevent the selection or acquisition of resistance mutations toward tyrosine kinase inhibitors.
2019-11-22 | PRD000749 | Pride