Project description:<p>Therian mammals and angiosperms evolved genomic imprinting in nutritive tissues, the placenta and endosperm, where maternal and paternal genomes are in conflict with respect to resource allocation. In imprinted genes, transcription is repressed from either the paternal or the maternal allele, resulting in allele specific expression (ASE). We studied variation in ASE of imprinted genes in human placentas to detect loss of imprinting (LOI), which refers to departures from mono-allelic expression. The placental tissue was collected in connection with a multigenerational, prospective cohort study in Mali, West Africa, in which individuals were followed from infancy and early childhood to adulthood (age 18+ years). When young women for whom we had longitudinal growth data gave birth, we collected placental tissue and umbilical cord tissue. We genotyped the umbilical cord tissue and saliva samples from parents using targeted DNAseq to identify SNPs in 96 genes known from the literature to be imprinted in human placentas. We used RNAseq to analyze allele specific expression of the heterozygous SNPs. Our results provide the first systematic analysis of variation in LOI across genes and individuals and make it possible to test the hypothesis that modulation of imprinting is an epigenetic mechanism that contributes to the regulation of offspring growth. </p>
Project description:The purpose of the experiment was to compare placental transcriptome of rhesus macaque at approximately 80% completed gestation to human placental transcriptomes.
Project description:Maternal obesity is becoming a major health consideration for successful pregnancy outcomes. There is growing proof that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are so far poorly understood. We set out to analyse term placenta whole transcriptome in obese (n=5) and normoweight women (n=5), using Affymetrix microarray platform compromising of 50,000 probe sets. Our analysis shows that the placental transcriptome differs between normoweight and obese women. Different processes and pathways among placenta from obese women were dysregulated, including inflammation and immune responses, lipid metabolism, cell death and survival and cancer pathways, vasculogenesis and angiogenesis, and glucocorticoid receptor signaling pathway. Together, this global gene expression profiling approach demonstrates and confirms that maternal obesity creates a unique in utero environment that impairs placental transcriptome.
Project description:Whole-transcriptome profiles of individual human placental villi samples from twenty-five (25) Indian women with normal pregnancies during 6- to 8-weeks of gestation were examined using human whole genome expression arrays (NimbleGen 135K). The present study focused on the whole-transcriptome profiling using NimbleGen135K (070925_HG18_exp__12X135K) human whole genome expression arrays of individual human placental villi samples obtained from twenty-five (25) proven-fertile women bearing normal pregnancies voluntarily terminated between 6- and 8-weeks of gestation. Gestational age was estimated from menstrual history, physical and ultrasonographic evaluation. No case of complicated pregnancy from infection, and other significant fetal and maternal clinical indications was included. These twenty five (25) samples include biological replicates of 6, 7 and 8 weeks placental villi samples.
Project description:Background: Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. Results: We estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%). Conclusion: We apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection. Placental mRNA was sequenced on an Illumina GAIIx. Samples were derived from 4 human groups, 10 individuals per group, 2 samples per individual