Purpose: Age-related degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE)/choroid from early AMD and control maculas using exon-based arrays. Methods: Gene expression levels in nine early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using DAVID, and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. CFH genotype was also assessed and differential expression was analyzed with respect to high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Results: Seventy-five genes were identified as differentially expressed (raw p-value < 0.01; >50% fold change, mean log2 expression level in AMD or control median of all average gene expression values); however, no genes were significant (adj. p-value < 0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change < 0.5; raw p-value < 0.01), 18 genes were identified by DAVID analysis as associated with vision or neurological processes. GSEA of RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis with respect to CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p-value = 0.0008). Conclusions: GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout occurs early in the pathogenesis of AMD.
Altered gene expression in dry age-related macular degeneration suggests early loss of choroidal endothelial cells.
Sex, Age, Specimen part
View SamplesRhoBTB2 is a novel Rho GTPase that undergoes loss, underexpression and mutation in breast and lung cancer. We have shown that we can mimic loss of RhoBTB2 through siRNA treatment of primary cells. We propose to perform comparative microarray analysis of primary lung cells to establish the identification of the gene targets of RhoBTb2 regulation.
The atypical Rho GTPase RhoBTB2 is required for expression of the chemokine CXCL14 in normal and cancerous epithelial cells.
No sample metadata fields
View SamplesIn many parts of the US, selenium (Se)-deficient soils dictate the necessity of supplementing this trace mineral directly to the diet of cattle, with the form of Se supplied known to affect tissue-level gene expression profiles and presumably function. Because a deficiency of Se will reduce fertility, including reduced biosynthesis of testosterone by the testis and an increased frequency of abnormalities in mature spermatozoa, we hypothesized that the form of Se supplemented to cows during gestation would affect the transcriptome of the neonatal bull calf testis. Microarray analysis using the Bovine gene 1.0 ST array (GeneChip; Affymetrix, Inc., Santa Clara, CA) was conducted to determine whether gestational form of supplemental Se affected gene expression profiles in the testis. GeneChip transcript annotations were last updated in January 2013 using the annotation update release 33 from the NetAffx annotation database.
Gestational form of Selenium in Free-Choice Mineral Mixes Affects Transcriptome Profiles of the Neonatal Calf Testis, Including those of Steroidogenic and Spermatogenic Pathways.
Specimen part
View SamplesHeterotopic cardiac transplants were constructed in male Wistar Furth (allograft donor) and ACI (host) rats. Rats were divided into three groups consisting of no treatment, treatment with a sub-therapeutic dose of cyclosporin A, and treated with combination of a sub-therapeutic dose of cyclosporin A and allochimeric peptide. The allografts were harvested at defined periods post-transplantation and RNA was harvested to monitor gene expression changes resulting from the various treatments in T-cells and in heart cells.
Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model.
Sex, Specimen part
View SamplesA number of breast or colon specific genes predictive of the relapse status were used in comparing the outcome from matched fresh frozen and stored in RNAlater preservative.
Prognostic gene expression signatures can be measured in tissues collected in RNAlater preservative.
No sample metadata fields
View SamplesHistologic diagnosis of T cell-mediated rejection in kidney transplant biopsies has limited reproducibility because it is based on non-specific lesions using arbitrary rules that are subject to differing interpretations. We used microarray results from 403 indication biopsies previously given histologic diagnoses to develop a molecular classifier that assigned a molecular T cell-mediated rejection score to each biopsy. Independent assessment of the biopsies by multiple pathologists confirmed considerable disagreement on the presence of TCMR features: 79-88% accuracy and 35-69% sensitivity. The agreement of the molecular T cell-mediated rejection score with the histology diagnosis was similar to agreement among individual pathologists: accuracy 89%, sensitivity 51%. However, the score also predicted the consensus among pathologists, being highest when all agreed. Many discrepancies between the scores and the histologic diagnoses were in situations where histology is unreliable e.g. scarred biopsies. The score correlated with histologic lesions and gene sets associated with T cell-mediated rejection. The transcripts most often selected by the classifier were expressed in effector T cells, dendritic cells, or macrophages or inducible by interferon-gamma. Thus the T cell-mediated rejection score offers an objective assessment of kidney transplant biopsies, predicting the consensus opinion among multiple pathologists, and offering insights into underlying disease mechanisms.
Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies.
Disease
View SamplesAlternative mRNA splicing is the main reason vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription and the rate of transcript elongation has a profound effect on splicing. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle that represents its functional form, and the composition of which determines the fate of the mature transcript4. However, factors that connect the transcribing polymerase with the mRNP particle and help integrate transcript elongation with mRNA splicing remain obscure. Here, we characterized the interactome of chromatin-associated mRNP particles and thereby identified Deleted in Breast Cancer 1 (DBC1) and a protein we named ZIRD. These proteins are subunits of a novel protein complex, named DBIRD, which binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in A/T-rich DNA, and is present at the affected exons. RNAi-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. These data indicate that DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with regulation of alternative splicing.
DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation.
Cell line
View SamplesTo amass candidate DIMM targets in addition to Phm (Park et al., 2008a), we used genome-wide microarray profiling by over-expressing DIMM throughout the embryonic nervous system. We compared profiles from experimental (elav>dimm) and control (elav-GAL4) embryos at 22-26 hr and 28-32 hr after egg laying (AEL). The design was intended to identify transcripts consistently up-regulated shortly after the induction of DIMM; in so doing, we could circumvent the lethality that ensues in late embryonic, and/ or by early larval stages, due to pan-neuronal DIMM expression.
Molecular organization of Drosophila neuroendocrine cells by Dimmed.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Lymphocyte DNA methylation mediates genetic risk at shared immune-mediated disease loci.
Sex, Age, Specimen part, Subject
View SamplesGene expression profile in circulating leukocytes identifies patients with coronary artery disease
Gene expression patterns in peripheral blood correlate with the extent of coronary artery disease.
Sex, Age, Specimen part, Race
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