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Homo sapiens
382 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
Oxidized phospoholipids are a pro-inflammatory component of minimally modified lipoproteins that get trapped in the subendothelial space of atherosclerotic plaques of large arteries. To model the response of endothelial cells in a pro-atherosclerotic enviroment we measured the expression in primary endothelial cells with and without treatment with oxidized phsopolipids from 96 genetically identical donors of anonymous origin.
Publication Title
Systems genetics analysis of gene-by-environment interactions in human cells.
Sample Metadata Fields
Sex, Subject
View Samples- Homo sapiens
- 362 Downloadable Samples
Illumina HiSeq 2000
Description
The genetics of messenger RNA expression has been extensively studied in humans and other organisms, but little is known about genetic factors contributing to microRNA (miRNA) expression. We examined natural variation of miRNA expression in adipose tissue in a population of 200 men who have been carefully characterized for metabolic syndrome phenotypes as part of the METSIM study. We genotyped the subjects using high-density SNP microarrays and quantified the mRNA abundance using genome-wide expression arrays and miRNA abundance using next generation sequencing. We reliably quantified 356 miRNA species that were expressed in human adipose tissue, a limited number of which made up most of the expressed miRNAs. We mapped the miRNA abundance as an expression quantitative trait and determined cis regulation of expression for 9 of the miRNAs and of the processing of one miRNA (miR-28). The degree of genetic variation of miRNA expression was substantially less than that of mRNAs. For the majority of the miRNAs, genetic regulation of expression was independent of the host mRNA transcript expression. We also showed that for 108 miRNAs, mapped reads displayed widespread variation from the canonical sequence. We found a total of 24 miRNAs to be significantly associated with metabolic syndrome traits. We suggest a regulatory role for miR-204-5p which was predicted to inhibit ACACB, a key fatty acid oxidation enzyme that has been shown to play a role in regulating body fat and insulin resistance in adipose tissue. Overall design: miRNA expression profiling of adipose tissue isolated from 200 humans
Publication Title
Genetic regulation of human adipose microRNA expression and its consequences for metabolic traits.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Oxidized phospholipids are thought to promote atherogenesis by stimulating endothelial cells (ECs) to produce inflammatory cytokines, such as IL-8. In studies with mouse models, we previously demonstrated that genetic variation in inflammatory responses of endothelial cells to oxidized lipids contributes importantly to atherosclerosis susceptibility. We now show that similar variations occur in cultured aortic ECs derived from multiple heart transplant donors. These variations were stably maintained between passages and, thus, reflect either genetic or epigenetic regulatory differences. Expression array analysis of aortic EC cultures derived from 12 individuals revealed that >1,000 genes were regulated by oxidized phospholipids. We have used the observed variations in the sampled population to construct a gene coexpression network comprised of 15 modules of highly connected genes. We show that several identified modules are significantly enriched in genes for known pathways and confirm a module enriched for unfolded protein response (UPR) genes using siRNA and the UPR inducer tunicamycin. On the basis of the constructed network, we predicted that a gene of unknown function (MGC4504) present in the UPR module is a target for UPR transcriptional activator ATF4. Our data also indicate that IL-8 is present in the UPR module and is regulated, in part, by the UPR. We validate these by using siRNA. In conclusion, we show that interindividual variability can be used to group genes into pathways and predict gene-gene regulatory relationships, thus identifying targets potentially involved in susceptibility to common diseases such as atherosclerosis.
Publication Title
Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids.
Sample Metadata Fields
Cell line, Subject
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GSE38705- Mus musculus
- 510 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Identify genes involved in regulation of inflammatory responses and gene-environemnt interactions, in macrophages from a set of mouse inbred strains termed the HMDP. The HMDP is a genetically diverse mapping panel comprised of classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Bennett et al Genome Research 2010.
Publication Title
Unraveling inflammatory responses using systems genetics and gene-environment interactions in macrophages.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 872 Downloadable Samples
Affymetrix HT Mouse Genome 430A Array (htmg430a), Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genetic architecture of insulin resistance in the mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 439 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a), Illumina MouseRef-8 v2.0 expression beadchip
Description
Identify genes in the gonadal adipose tissue whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Publication Title
Genetic architecture of insulin resistance in the mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 433 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a), Illumina MouseRef-8 v2.0 expression beadchip
Description
Identify genes in the liver whose expression is under genetic regulation in the Hybrid Mouse Diversity Panel (HMDP). The HMDP comprises classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Parks et al Cell Metabolism 2015. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Publication Title
Genetic architecture of insulin resistance in the mouse.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 288 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Novel, systems-based approach to mouse genetics.
Publication Title
A high-resolution association mapping panel for the dissection of complex traits in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 185 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
Identify genes in the epididymal adipose tissue whose expression is under genetic regulation in the hybrid mouse diversity panel. The hybrid mouse diversity panel is comprised of classical inbred and recombinant inbred wild type mice. The RMA values of genes were used for genome wide association as described in Bennett et al Genome Research 2010. These data are used to identify candidate genes at loci associated with obesity and dietary responsiveness.
Publication Title
Genetic control of obesity and gut microbiota composition in response to high-fat, high-sucrose diet in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 770 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
We analyzed samples from 770 male human subjects who are part of the METSIM study. Ethics Committee of the Northern Savo Hospital District approved the study. All participants gave written informed consent. The population-based cross-sectional METSIM study included 10 197 men, aged from 45 to 73 years, who were randomly selected from the population register of the Kuopio town in eastern Finland (population 95000). Every participant had a 1-day outpatient visit to the Clinical Research Unit at the University of Kuopio, including an interview on the history of previous diseases and current drug treatment and an evaluation of glucose tolerance and cardiovascular risk factors. After 12 h of fasting, a 2 h oral 75 g glucose tolerance test was performed and the blood samples were drawn at 0, 30 and 120 min. Plasma glucose was measured by enzymatic hexokinase photometric assay (Konelab Systems reagents; Thermo Fischer Scientific, Vantaa, Finland). Insulin was determined by immunoassay (ADVIA Centaur Insulin IRI no. 02230141; Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA). Height and weight were measured to the nearest 0.5 cm and 0.1 kg, respectively. Waist circumference (at the midpoint between the lateral iliac crest and lowest rib) and hip circumference (at the level of the trochanter major) were measured to the nearest 0.5 cm. Body composition was determined by bioelectrical impedance (RJL Systems) in subjects in the supine position.
Publication Title
Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples