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- W1994177501 abstract "Gestational diabetes predisposes offspring to obesity and metabolic disease later in life. However, the molecular basis for this developmental programming is poorly understood. A limited number of small studies have taken hypothesis driven and microarray approaches to characterizing placental gene expression profiling among diabetics. The aims of our study were to apply whole transcriptome RNA sequencing (RNA-Seq) in conjunction with robust computational analysis to investigate global placental gene expression among diabetic gravidae. Using systematic methodology in a nested cohort design (n=18), placental tissue and accompanying data were collected and tediously processed in a uniform fashion (flash frozen and stored at -80C). Purified fragmented mRNA was converted to ds-cDNA (random hexamer primers) for sequencing library builds (TrueSeq strandless on Illumina HiSeq 2000). Reads were mapped to the human genome (NCBI GRCh37/UCSC hg19) using TopHat. Genes demonstrating differential expression were identified following normalization (FPKM) as determined by Cuffdiff at an FDR-adjusted p-value of 0.05. Data were visualized using CummeRbund. In total, 1.15 mappable (79%) of 1.45 billion placental RNA sequence reads were analyzed. As anticipated, robust comparisons between caesarean (n=9) and vaginal (n=9) deliveries failed to demonstrate differential placental transcriptome profiles, while 7 of 8 male-specific genes mapped to the Y chromosome. Of interest, after controlling for multiiple comparisons and confounders, 6 novel gene pathways were found to be signficantly underexpressed in gestational diabetes (Figure). Our discovery based approach revealed findings novel to the placenta and gestational diabetes, including serum albumin (ALB) [diminished in serum of diabetics] and ARFIP2, TJP2, and KIAA0889 [differentially regulated in the liver of diabetics]. These findings may potentially advance our understanding of GDM pathogenesis." @default.
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- W1994177501 date "2013-01-01" @default.
- W1994177501 modified "2023-09-26" @default.
- W1994177501 title "56: Placental whole transcriptome analysis reveals significant differential gene expression patterns among term diabetic gravidae" @default.
- W1994177501 doi "https://doi.org/10.1016/j.ajog.2012.10.230" @default.
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