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Epigenome analysis of neonatal blood spots

ABSTRACT: Changes in DNA methylation, is one mechanism by which genes are regulated. Aberrant methylation can lead to gene dysregulation, such as inactivation of tumour suppressor genes, and is observed in all cancers. Gene dysregulation via aberrant DNA methylation may be an important contributor to disease outcomes. Importantly, these marks are malleable in response to environmental exposures and contribute to phenotypic plasticity in the context of a fixed genotype. Many studies suggest maternal exposures during pregnancy can have a profound impact on the epigenome and so determine gene expression patterns and health throughout the life-course. Studies of altered epigenetic marking are of profound importance for mechanistic understanding of the role of exposures on health but especially for studies of the developmental origins of health. Historically collected neonatal blood spot samples represent a rich resource in which methylation at birth could be measured decades after being sampled and methylation patterns associated with recorded disease outcomes. Here we aimed to test the feasibility that methylation could be assessed in historically collected blood spot samples and assess if the time since sample collection affected methylation patterns. The Newcastle Haematology biobank houses blood spots collected routinely from neonates 5-8 days after birth between the years 1984-1994 in the local region. Samples were selected from across the collection period and cross referenced with the Northern region Children's malignant disease registry in an aim to exclude samples from children who had gone on to have a malignancy during childhood. Genome-wide DNA methylation profiling of neonatal blood spots was assessed using the Illumina Infinium® MethylationEPIC BeadChip platform. Extraction yield DNA of sufficient quality and quantity for successful analysis of DNA methylation. Time since collection was not found to significantly influence methylation in this sample. Data from this study could be utilised in future case-controls studies to investigate the relationship between methylation patterns and birth and disease outcomes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211591 | GEO | 2024/12/13

REPOSITORIES: GEO

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Project description:Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from mothers enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/L). Changes in iAs-associated DNA 5-methyl cytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and were compared to corresponding expression levels and birth outcomes. In the context of arsenic exposure, a total of 2,705 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyzes identified DNA methylation changes that were most predictive of gene expression levels. Specifically, CpG methylation within CpG islands positioned within the first exon and 200bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of seven of these genes were associated with differences in birth outcomes including gestational age, placental weight and head circumference. These data highlight the complex interplay between DNA methylation and functional changes in gene expression and health outcomes and underscore the need for functional analyzes coupled to epigenetic assessments. 48 DNA methylation profiles were obtained but only 38 samples corresponding to samples also analyzed for gene expression (see Rager 2014) were further normalized and used in the publication from the Biomarkers of Arsenic (BEAR) cohort were analyzed for DNA methylation profiles.

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Epigenome analysis of neonatal blood spots

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