The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work.
Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association.
Specimen part
View SamplesThe goal of this study is to measure Arabidopsis mRNA transcription and mRNA decay rates genome wide at two temperatures, and thus to calculate the temperature coefficient of both processes. Sensing and response to ambient temperature is important for controlling growth and development of many organisms, in part by regulating mRNA levels. mRNA abundance can change with temperature, but it is unclear whether this results from changes to transcription or decay rates and whether passive or active temperature regulation is involved. Results Using a base analogue labelling method we directly measured the temperature coefficient (Q10) of mRNA synthesis and degradation rates of the Arabidopsis transcriptome. We show that for most genes transcript levels are buffered against passive increases in transcription rates by balancing passive increases in the rate of decay. Strikingly, for temperature-responsive transcripts, increasing temperature raises transcript abundance primarily by promoting faster transcription relative to decay and not vice versa, suggesting a global transcriptional mechanism process exists for the activethat controls of mRNA abundance by temperature/
Direct measurement of transcription rates reveals multiple mechanisms for configuration of the Arabidopsis ambient temperature response.
Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Decreased selenium-binding protein 1 in esophageal adenocarcinoma results from posttranscriptional and epigenetic regulation and affects chemosensitivity.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesHuman skin samples from cutaneous lupus subtypes, psoriasis, and normal patients were used to corroborate findings of Fas Ligand elevation in a murine model of cutaneous lupus
Fas ligand promotes an inducible TLR-dependent model of cutaneous lupus-like inflammation.
Specimen part, Disease, Disease stage
View SamplesSpecimens were collected from esophageal adenocarcinoma patients undergoing esophagectomy for adenocarcinoma at the University of Michigan Health System between 1991 and 2004. Written consent was obtained from each patient according to the approval and guidelines of the University of Michigan institutional review board. Patients receiving treatment with chemotherapy and/or radiotherapy prior to surgery were excluded.
Decreased selenium-binding protein 1 in esophageal adenocarcinoma results from posttranscriptional and epigenetic regulation and affects chemosensitivity.
Sex, Age, Specimen part, Disease, Disease stage, Race
View SamplesThe goal of this set of experiments was to identify transcripts that are differentially expressed upon reactivation of NMD in an nmd2::HIS3 strain by galactose-induced expression of the NMD2 gene.
Association of yeast Upf1p with direct substrates of the NMD pathway.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Correlated alterations in genome organization, histone methylation, and DNA-lamin A/C interactions in Hutchinson-Gilford progeria syndrome.
Sex, Specimen part, Disease, Cell line
View SamplesmRNA from wild-type (Cre-) and MLL1-deficient (Cre+) BMDMs were analyzed via gene chip (Mouse Gene ST 2.1, Affymetrix) for relative expression changes. Isolated mRNA from Cre- and Cre+ BMDMs stimulated with classical activation signals (IFNg, LPS or IFNg+LPS) was analyzed using a gene chip panel of >40,000 RefSeq transcripts, and resulting fold expression was determined by analyzing quality-controlled expression values for validated probesets.
The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages.
No sample metadata fields
View SamplesThoracic perivascular adipose tissue (PVAT) is a unique adipose depot that likely influences vascular function and susceptibility to pathogenesis in obesity and metabolic syndrome. Surprisingly, PVAT has been reported to share characteristics of both brown and white adipose, but a detailed direct comparison to interscapular brown adipose tissue (BAT) has not been performed. Here we show by full genome DNA microarray analysis that global gene expression profiles of PVAT are virtually identical to BAT, with equally high expression of Ucp-1, Cidea and other genes known to be uniquely or very highly expressed in BAT. PVAT and BAT also displayed nearly identical phenotypes upon immunohistochemical analysis, and electron microscopy confirmed that PVAT contained multilocular lipid droplets and abundant mitochondria. Compared to white adipose tissue (WAT), PVAT and BAT from C57BL/6 mice fed a high fat diet for 13 weeks had markedly lower expression of immune cell-enriched mRNAs, suggesting resistance to obesity-induced inflammation. Indeed, staining of BAT and PVAT for macrophage markers (F4/80, CD68) in obese mice showed virtually no macrophage infiltration, and FACS analysis of BAT confirmed the presence of very few CD11b+/CD11c+ macrophages in BAT (1.0%) in comparison to WAT (31%). In summary, murine PVAT from the thoracic aorta is virtually identical to interscapular BAT, is resistant to diet-induced macrophage infiltration, and thus may play an important role in protecting the vascular bed from thermal and inflammatory stress.
Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation.
Specimen part, Treatment
View SamplesDuring malaria infection is observed a robust immune response culminating on release of inflammatory mediators. This exacerbated immune response is involved in malaria symptoms and mortality. There are evidences that this response is mediated by innate immunity where pattern recognition receptors have a key role. We used microarrays to elucidate some pro-inflammatory genes that are differential expressed during P. chabaudi infection, a malarial murine model
Daily Rhythms of TNFα Expression and Food Intake Regulate Synchrony of Plasmodium Stages with the Host Circadian Cycle.
Sex, Age, Specimen part
View Samples