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. Overall design: Placental mRNA was sequenced on an Illumina GAIIx. Samples were derived from 4 human groups, 10 individuals per group, 2 samples per individual
Evaluating intra- and inter-individual variation in the human placental transcriptome.
No sample metadata fields
View SamplesThe first embryonic cell divisions rely on maternally stored mRNA and proteins. The zygotic genome is initially transcriptionally silenced and activated later in a process called zygotic genome activation (ZGA). ZGA in any species is still a poorly understood process; the timing of transcription onset is controversial and the identity of the first transcribed genes unclear. Zebrafish, Danio rerio, is a rapidly developing vertebrate model, which is accessible to experimentation and global studies before, during and after ZGA. Overall design: To accurately determine the onset of ZGA and to identify the first transcripts in zebrafish, we developed a metabolic labeling method, utilizing the ribonucleotide analog 4-thio-UTP, which allows efficient and specific affinity purification of newly transcribed RNA. Using deep sequencing, we characterized the onset of transcription in zebrafish embryos at 128-, 256-, and 512-cell stages. We identified 592 nuclear-encoded zygotically transcribed genes, comprising 670 transcript isoforms. Mitochondrial genomes were highly transcribed at all time points. Further, bioinformatic analysis revealed an enrichment of transcription factors and miRNAs among the newly transcribed genes, suggesting mechanistic roles for the early genes that are required to activate subsequent gene expression programs in development. Interestingly, analysis of gene-architecture revealed that zygotically transcribed genes are often intronless and short, reducing transcription and processing time of the transcript. The newly generated dataset enabled us to compare zygotically transcribed genes over a broad phylogenetic distance with fly and mouse early zygotic genes. This analysis revealed that short gene length is a common characteristic for early zygotically expressed genes. However, we detected a poor level of overlap for shared orthologs.
The earliest transcribed zygotic genes are short, newly evolved, and different across species.
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View SamplesAim of this project was to determine the transcriptional response of the isolate PA30 to tap water and waste water.
Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water.
Specimen part
View SamplesAim of this project was to determine the transcriptional response of the isolate PA49 to tap water and waste water.
Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant Pseudomonas aeruginosa isolates exposed to waste water and tap water.
Specimen part
View SamplesColon cancers typically contain tumor cell populations with differential WNT signaling activity. Colon cancer cells with high WNT-activity have been attributed increase tumorigenic potential and stem cell characteristics.
Differential WNT activity in colorectal cancer confers limited tumorigenic potential and is regulated by MAPK signaling.
Specimen part, Cell line
View SamplesLow-dose epirubicin at non-cytotoxic doses down regulated NLRP3 inflammasome components and reduced the release of proinflammatory cytokines.
Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Sex, Specimen part
View SamplesProfiling of gene expression in Vastus Lateralis from female patients before and after GBP surgery and from lean Control
Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.
Sex, Specimen part
View SamplesThe aim of the study was to identify in vivo spermatogonial gene expression within the context of their biological niche.
Screening for biomarkers of spermatogonia within the human testis: a whole genome approach.
Specimen part
View SamplesAbstract: Colonic cancers with a serrated morphology have been proposed to comprise a molecularly distinct tumor entity following an alternative pathway of genetic alterations independently of APC mutations. Here we demonstrate that intestinal cell specific expression of oncogenic K-rasG12D in mice induces serrated hyperplasia, which is characterized by p16ink4a overexpression and induction of senescence. Deletion of Ink4a/Arf in K-rasG12D expressing mice prevents senescence and leads to invasive, metastasizing carcinomas with morphological and molecular alterations comparable to human KRAS mutated serrated tumors. Thus, we suggest that oncogenic K-ras is sufficient to initiate an alternative, serrated pathway to colorectal cancer and hence propose RAS-RAF-MEK signaling apart from APC as an additional gatekeeper in colorectal tumor development.
Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis.
Specimen part
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