Project description:Genome wide DNA methylation profiling of umbilical cord blood DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 470 cord blood samples from infants born to women in the Southampton Women's Survery (SWS) cohort, to examine the association between DNA methylation in the infant and aspects of health and disease in early and life and childhood.
Project description:Genome-wide DNA methylation profiling of umbilical cord blood buffy coat DNA samples. The Illumina Infinium MethylationEPIC array was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Samples included 557 cord blood samples born to obese women in the UPBEAT trial, with and without gestational diabetes mellitus (GDM), to determine the association between maternal GDM and hyperglycaemia during pregnancy on the methylation in the infant.
Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu. Umbilical cord blood was drawn into Tempus Blood RNA tubes (Applied Biosystems) from children born between January and May 2010 at the maternity unit of Jorvi hospital (Espoo, Finland; n=48), maternity units of Tartu and PM-CM-5lva (Estonia; n=25), or two maternity departments in Petrozavodsk (capital of the Republic of Karelia, Russian Federation; n=40) according to the manufacturerM-BM-4s protocol and then stored in M-bM-^HM-^R70 M-BM-0C until analyzed. All newborn infants were full-term (>36 gestational weeks) and born vaginally. 113 cord blood RNA samples were analyzed with Affymetrix U219 gene array. Gender, pregnancy week, month of birth and HLA risk class were included as confounding factors in the analysis model.
Project description:The prevalence of immune-mediated diseases such as allergies and autoimmune diseases is on the rise in the developed world. Microbial exposure is known to modulate the risk for these diseases. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from full-term newborn infants born with normal vaginal delivery in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economical conditions). Transcriptomic profiles were analyzed using whole genome microarrays including gender, gestational age, birth month and HLA allele genotype as confounding variables in the analysis. The data revealed that the whole blood transcriptome of Finnish and Estonian neonates differ from their Karelian counterparts. Samples from Karelian infants had an increase in transcripts associated with LPS induction and bacterial sepsis observed in 1-year-old infants in earlier studies. The results suggest exposure to toll like receptor (TLR) ligands and a more matured immune response in infants born in Petrozavodsk compared to the Finnish and Estonian infants. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation of both the adaptive and the innate immune responses in accordance with the surrounding microbial milieu.
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight and estímate blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Peripheral blood DNA (at days 14 and 28) from preterm neonates that went on to develop BPD (n = 14) or not (nonBPD, n = 93) was applied to Illumina EPIC methylation arrays. Using DNA methylation analysis of cord blood DNA, we investigated association of GA and birth weight with the estimated distribution of cord blood cell types, particularly the nucleated red blood cell (NRBC) in a pilot-size cohort of preterm infants with or without BPD. We describe changes in methylation-based estimates of blood cell-type composition in relation to GA and birth weight. After adjusting for covariates (GA, birth weight, cell type proportions, etc.) we identify differentially methylated CpGs and genes associated with BPD at different time points.
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight and estímate blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD. Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (nonBPD, n = 93) was applied to Illumina 450K methylation arrays. Using DNA methylation analysis of cord blood DNA, we investigated association of GA and birth weight with the estimated distribution of cord blood cell types, particularly the nucleated red blood cell (NRBC) in a pilot-size cohort of preterm infants with or without BPD. We describe changes in methylation-based estimates of blood cell-type composition in relation to GA and birth weight. After adjusting for covariates (GA, birth weight, cell type proportions, etc.) we identify differentially methylated CpGs and genes associated with BPD.
Project description:The rate of cesarean delivery (CD) in China has risen sharply and the high rate was reported to be associated with increased risk of disease in the offspring. However, there is little research on the molecular mechanism of critical pathways and gene signatures involved in the neonatal immunity of cesarean-born infants. This study was undertaken to identify unique gene signatures which was involved in the neonatal immunity of cesarean-born infants through large-scale RNA-sequencing. Genes differentially expressed in cesarean-born infants were identified and further validated through quantitative real-time PCR (RT-qPCR). Moreover, we employed weighted gene co-expression network analysis (WGCNA) to identify highly connected genes that were correlated with neonatal inflammation. In total, 73 differentially expressed genes (DEGs) were identified between cesarean-born infants and normal vagina childbirth. The results obtained by secondary validation indicated that GATM, MIF, IFI27, IL1B, CA1, and EPHB1 were significantly upregulated in phenotype CD, while CYP2A6 and DLK1 were significantly down regulated. Further, functional and pathway enrichment analysis reveals perturbation of several DEGs involved in signaling pathways pertaining to immunoregulation, inflammation, apoptosis, and nervous development. Additionally, HLA-DOB popped out as a core gene in the process of inflammation, which might indicate the risk of cesarean-born infants for inflammatory disease. Notably, our study for the first time has documented gene signatures PIK3CA, PTPRC, SOS1, IL6ST, and MALT1, which were found to be involved in neonatal inflammation. Taken together, the full expression repertoire including the differentially expressed gene sets and core differentially co-expressed genes should provide an excellent resource for identifying potential biomarkers of cesarean-born infants with inflammation, and formulating new hypotheses for physiological functions and the discovery of novel therapeutic targets for inflammatory disease.
Project description:Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD haves been increased. Therapeutic options are limited for prevention and treatment. This study was designed to explore differentially expressed genes associated with BPD. Cord blood mRNA from preterm neonates that went on to develop BPD (n = 6) or not (nonBPD, n = 17) was applied to Illumina HumanHT-12 arrays, we identify differentially expressed genes associated with BPD.
Project description:Genome wide DNA methylation profiling of umbilical cord blood DNA samples using the Illumina Infinium MethylationEPIC array (approximately 850,000 CpGs). Samples included cord blood samples from infants born to women with (exposed) and without (control) infection with Trypanosoma cruzi parasites, to test for a potential epigenetic effect of in utero exposure to maternal infection.