Overexpression of VEGF (vascular endothelial growth factor) in the germinal matrix of the brain causes GMH-IVH-like anomalies (Germinal matrix hemorrhage [GMH]; intraventricular hemorrhage [IVH]).
Overexpression of vascular endothelial growth factor in the germinal matrix induces neurovascular proteases and intraventricular hemorrhage.
Specimen part
View SamplesGene expression levels are determined by the balance between rates of mRNA transcription and decay, and genetic variation in either of these processes can result in heritable differences in transcript abundance. Although the genetics of gene expression has been the subject of intense interest, the contribution of heritable variation in mRNA decay rates to gene expression variation has received far less attention. To this end, we developed a novel statistical framework and measured allele-specific differences in mRNA decay rates in a diploid yeast hybrid created by mating two genetically diverse parental strains. In total, we estimate that 31% of genes exhibit allelic differences in mRNA decay rate, of which 350 can be identified at a false discovery rate of 10%. Genes with significant allele-specific differences in mRNA decay rate have higher levels of polymorphism compared to other genes, with all gene regions contributing to allelic differences in mRNA decay rate. Strikingly, we find widespread evidence for compensatory evolution, such that variants influencing transcriptional initiation and decay having opposite effects, suggesting steady-state gene expression levels are subject to pervasive stabilizing selection. Our results demonstrate that heritable differences in mRNA decay rates are widespread, and are an important target for natural selection to maintain or fine-tune steady-state gene expression levels. Overall design: We measured rates of allele-specific mRNA decay (ASD) in a diploid yeast produced by mating two genetically diverse haploid Saccharomyces cerevisiae strains: the laboratory strain BY4716 (BY), which is isogenic to the reference sequence strain S288C, and the wild Californian vineyard strain RM11-1a (RM). Briefly, we introduced rpb1-1, a temperature sensitive mutation in an RNA polymerase II subunit, to each of the haploid yeast strains, mated the strains, and grew the resulting hybrid diploid to mid-log phase at 24 °C, before rapidly shifting the culture to 37 °C to inhibit transcription. RNA-seq was performed on culture samples taken at 0, 6, 12, 18, 24, and 42 minutes subsequent to the temperature shift. To identify ASD, we used transcribed polymorphisms to distinguish between parental transcripts, and compared the relative levels of transcript abundance over the time course. Note, this experimental design internally controls for trans-acting regulatory variation as well as environmental factors. Under the null hypothesis of no ASD, the proportion of reads from the BY transcript (p_BY = N_BY / (N_BY + N_RM)) observed over the time course remains unchanged. However, genes with ASD will exhibit an increasing or decreasing proportion of BY reads as a function of time. In total, we measured ASD from three independent biological replicates.
Heritable variation of mRNA decay rates in yeast.
Disease, Cell line, Subject
View SamplesWe report the transcriptome changes that result of the genomic deletion of one or two alleles of an islet-specific long non-coding RNA (Blinc1) in isolated pancreas from e15.5 mouse embryos. Overall design: Pancreas from e15.5 embryos were dissected and total RNA extracted. Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the mouse genome (UCSC/mm9) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq.
βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function.
Specimen part, Subject
View SamplesAdjacent alternative 3’ splice sites, those separated by =18nt, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron''s 3'' end depends upon sequence elements that define the branchpoint, polypyrimidine tract and terminal AG dinucleotide. Starting with RNA-seq data from germline-enriched and somatic cell-enriched C. elegans samples, we identify hundreds of introns with adjacent alternative 3’ splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is mono-directional, with somatic cells preferring to splice at the distal 3'' splice site and germline cells showing a distinct shift towards usage of the adjacent proximal 3'' splice site. Splicing patterns in somatic cells follow consensus rules of 3’ splice site definition, using sites with a short stretch of pyrimidines and an AG dinucleotide. Splicing in germline cells occurs at proximal 3'' splice sites that frequently lack a polypyrimidine tract or, occasionally, the AG dinucleotide. We provide evidence that use of germline-specific proximal 3'' splice sites is conserved across Caenorhabditis species. We propose that divergent mechanisms exist between germline and somatic cells in determining an intron terminus at adjacent alternative 3’ splice sites. Overall design: Examination of alternative splicing changes between germline- and somatic-cell enriched samples as well as nonsense-mediated decay mutants.
Coordinated tissue-specific regulation of adjacent alternative 3' splice sites in C. elegans.
Specimen part, Cell line, Subject
View SamplesIn a randomized controlled dietary intervention study we compared an isocaloric Healthy Nordic diet with the average Nordic diet for influence on abdominal subcutaneous adipose tisse gene expression. We studied obese adults with features of the metabolic syndrom, n=56. There was no significant difference in age, BMI, or gene expression between the groups before the intervention. The intervention lasted for 18-24 weeks.
Healthy Nordic diet downregulates the expression of genes involved in inflammation in subcutaneous adipose tissue in individuals with features of the metabolic syndrome.
Age, Specimen part
View SamplesIn response to WRKY40 and WRKY60 perturbation (and high light stress), significant transcriptional re-programming occurs particularly for genes encoding stress responsive mitochondrial and choloplast proteins.
AtWRKY40 and AtWRKY63 modulate the expression of stress-responsive nuclear genes encoding mitochondrial and chloroplast proteins.
Specimen part, Treatment
View SamplesThis study investigated the use of three different established cell sorting strategies to isolate and characterize stem cells from head and neck cancer cell lines.
Isolation and genomic characterization of stem cells in head and neck cancer.
Cell line
View SamplesLow passage head and neck squamous cancer cells (UT-14-SCC) were injected into the flanks of female nu/nu mice to generate xenografts. After tumors reached a size of 500mm3, they were treated with either sham RT or 15 Gy in one fraction.
Gene expression changes during repopulation in a head and neck cancer xenograft.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global DNA Hypomethylation in Epithelial Ovarian Cancer: Passive Demethylation and Association with Genomic Instability.
Sex, Age, Specimen part, Disease stage
View SamplesComparison of DNA methylome, mRNA transcriptome, and copy number variation in tumors with global loss of DNA methylation to tumors with normal global methylation.
Global DNA Hypomethylation in Epithelial Ovarian Cancer: Passive Demethylation and Association with Genomic Instability.
Sex, Age, Specimen part, Disease stage
View Samples