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Series GSE121582 Query DataSets for GSE121582
Status Public on Oct 23, 2018
Title Prenatal alcohol exposure: profiling developmental DNA methylation patterns in central and peripheral tissues
Organism Rattus norvegicus
Experiment type Methylation profiling by high throughput sequencing
Summary Prenatal alcohol exposure (PAE) alters the development of neurobiological systems, leading to lasting neuroendocrine, neuroimmune, and neurobehavioral deficits. Although the etiology of this reprogramming remains unknown, emerging evidence suggests DNA methylation as a potential mediator and biomarker for the effects of PAE due to its responsiveness to environmental cues and relative stability over time. Here, we utilized a rat model of PAE to examine the DNA methylation profiles of rat hypothalami and leukocytes at four time points during early development to assess the genome-wide impact of PAE on the epigenome and identify potential biomarkers of PAE. Our model of PAE approximates to 1-2x the legal limit of drunk driving in most jurisdictions (blood alcohol 80-150 mg/dl) throughout the equivalent of the first two trimesters of human pregnancy. Hypothalami were analyzed on postnatal (P) days 1, 8, 15, 22 and leukocytes at P22 to compare central and peripheral markers. Genome-wide DNA methylation analysis was performed by methylated DNA immunoprecipitation followed by next-generation sequencing. PAE resulted in lasting changes to DNA methylation profiles across all four ages, with 118 differentially methylated regions (DMRs) displaying persistent alterations across the developmental profile at a false-discovery rate (FDR) <0.05. By contrast, 299 DMRs showed the same direction of change in the hypothalamus and leukocytes of P22 pups at an FDR<0.05, with some genes overlapping with the developmental profile findings. The majority of these DMRs were located in intergenic regions, which contained several computationally-predicted transcription factor binding sites. Differentially methylated genes were generally involved in immune function, epigenetic remodeling, metabolism, and hormonal signaling, as determined by gene ontology analyses. Persistent DNA methylation changes in the hypothalamus may be associated with the long-term deficits observed in PAE. Furthermore, correlations between epigenetic alterations in peripheral tissues and those in the brain will provide a foundation for the development of biomarkers of fetal alcohol spectrum disorder (FASD). Finally, findings from studies of PAE provide important insight into the etiology neurodevelopmental and mental health disorders, as they tend to share numerous symptoms and comorbidities.
Overall design DNA methylation data from meDIP-seq of 60 rat samples, spanning three prenatal treatment groups (control, pair-fed, prenatal alcohol exposed), four ages (postnatal days 1, 8, 15, 22), and two tissues (hypothalamus [all ages], white blood cells [P22 only]). WBC and hypothalamic samples were obtained from the same animal on P22. Each group/tissue/age had n= 4. Two sequencing runs were performed for each sample (120 aligned bam files) and DNA methylation peaks were called using MACS2 following DNA processed (peak files).
Contributor(s) Lussier AA, Bodnar TS, Mingay M, Morin AM, Hirst M, Kobor MS, Weinberg J
Citation(s) 30568673
Submission date Oct 22, 2018
Last update date Jan 22, 2019
Contact name Michael S. Kobor
Organization name Centre for Molecular Medicine and Therapeutics / University of British Columbia
Department Medical Genetics
Lab Kobor
Street address 950 West 28th Avenue
City Vancouver
State/province BC
ZIP/Postal code V5Z 4H4
Country Canada
Platforms (1)
GPL14844 Illumina HiSeq 2000 (Rattus norvegicus)
Samples (60)
GSM3439617 P22-wbc-C14
GSM3439618 P0-hyp-C3
GSM3439619 P8-hyp-C7
BioProject PRJNA497836
SRA SRP166299

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Supplementary file Size Download File type/resource
GSE121582_RAW.tar 328.1 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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