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- W2051213825 abstract "To use a genome-wide cytosine methylation to identify regions of interest linking adverse intrauterine environment with metabolic abnormalities later in life SD dams were fed 1 of 3 diets: standard chow (Con), calorie restricted (pair-fed 60% kcal/d) from gestational day 11 through lactation (CR) or western diet from 3 wks old through gestation/lactation (WD). Litters culled to 8 were fed standard chow post weaning. MPS-based HELP-tagging assay was used to examine cytosine methylation levels at >1.6 million loci in the liver of female offspring at 9 wks from Con, CR, WD and aged female controls at 19-20 months (Old), n=6/grp. Differentially methylated regions (DMRs) were defined to provide targets likely to have relevant biological consequences using ‘dmrFind’ function in R package ‘charm’. Genes mapped to DMRs were uploaded to GSEA (Broad Institute) to determine ontology and pathway enrichment. DMRs influence on gene expression was performed using qPCR. Cases (CR/WD) compared to Con showed DMRs with enrichment for MAPK signaling pathway. The genome-wide approach was validated by expression changes in 2 DMR genes CACNA1D and PRKCB from MAPK signaling pathway, and 1 published gene associated with obesity, PC. Statistically significant decrease in expression was found for these genes in Cases compare to Con. A similar pattern of expression in these genes was seen in Old compared to Con as previous clustering analysis based on single loci indicates that Cases have methylation profiles most closely related to Old than Con. Regions of differential methylation may be identified using a genome wide approach as a discovery platform in genes that may link intrauterine environment to metabolic health later in life. Further validation of other DMRs may provide insight into the mechanisms responsible for developmental programming but our early analysis and preliminary data suggest that premature aging can be involved in the increase of sensitivity observed with adverse intrauterine environment." @default.
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- W2051213825 date "2014-01-01" @default.
- W2051213825 modified "2023-09-23" @default.
- W2051213825 title "810: Differentially methylated Regions as targets of adverse intrauterine environment" @default.
- W2051213825 doi "https://doi.org/10.1016/j.ajog.2013.10.843" @default.
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