We used expression quantitative trait locus mapping in the laboratory rat (Rattus norvegicus) to gain a broad perspective of gene regulation in the mammalian eye and to identify genetic variation relevant to human eye disease. Of >31,000 gene probes represented on an Affymetrix expression microarray, 18,976 exhibited sufficient signal for reliable analysis and at least 2-fold variation in expression among 120 F2 rats generated from an SR/JrHsd x SHRSP intercross. Genome-wide linkage analysis with 399 genetic markers revealed significant linkage with at least one marker for 1,300 probes (alpha = 0.001; estimated empirical false discovery rate = 2%). Both contiguous and noncontiguous loci were found to be important in regulating mammalian eye gene expression. We investigated one locus of each type in greater detail and identified putative transcription-altering variations in both cases. We found an inserted cREL binding sequence in the 5' flanking sequence of the Abca4 gene associated with an increased expression level of that gene, and we found a mutation of the gene encoding thyroid hormone receptor beta 2 associated with a decreased expression level of the gene encoding short-wave sensitive opsin (Opn1sw). In addition to these positional studies, we performed a pairwise analysis of gene expression to identify genes that are regulated in a coordinated manner and used this approach to validate two previously undescribed genes involved in the human disease Bardet-Biedl syndrome. These data and analytic approaches can be used to facilitate the discovery of additional genes and regulatory elements involved in human eye disease.
Regulation of gene expression in the mammalian eye and its relevance to eye disease.
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View SamplesThis sample is part of a study that compares small sample amplification technologies. The analysis looks at differential gene expression when compared to one round of T7 amplification. A tumor cell line was used in comparison to a human reference RNA in this study.
Big results from small samples: evaluation of amplification protocols for gene expression profiling.
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View SamplesTo examine molecular mechanisms of aortic valve stenosis in mice with hypertension and hypercholesterolemia, RNA-Seq was used during the developmental phase of stenosis to identify new gene targets. Overall design: Four groups of mice were studied: controls (CON), hypertensive (HT), hypercholesterolemic (HC), and HC/HT. Transgenic mice overexpressing human renin and human angiotensinogen served as the HT model and ApoE knockout mice served as the HC model. A sample size of N=4 was used for each of the four groups.
Fibrotic Aortic Valve Stenosis in Hypercholesterolemic/Hypertensive Mice.
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View SamplesProstate cancer is dependent on androgen receptor (AR) signaling at all stages of the disease and cyclin D1 has been shown to negatively modulate the expression of the AR-dependent gene prostate specific antigen (KLK3/PSA).
Cyclin D1 is a selective modifier of androgen-dependent signaling and androgen receptor function.
Cell line, Treatment
View SamplesGene expression profiling of three PEL cell lines compare to three Burkitt's lymphoma lines to figure out the changed genes under KSHV latent infection.
The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest.
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View SamplesThe Long Evans/orl (LE/orl) rat is an animal model of inherited undescended testis (UDT). To explore genetic mechanisms of UDT, we studied differential gene expression in LE/orl and LE wild type (LE/wt) fetal gubernaculum and testis.
Altered expression of muscle- and cytoskeleton-related genes in a rat strain with inherited cryptorchidism.
Sex, Specimen part
View SamplesDuctal carcinoma in situ (DCIS) is a precursor lesion that can give rise to invasive breast cancer (IBC). It has been proposed that both the nature of the lesion and the tumor microenvironment play key roles in progression to IBC. Here, laser capture microdissected tissue samples from epithelium and stroma in normal breast, pure DCIS, and pure IBC were employed to define key gene expression profiles associated with disease progression.
Progression of ductal carcinoma in situ to invasive breast cancer is associated with gene expression programs of EMT and myoepithelia.
Specimen part, Subject
View SamplesBackground: Extended hepatectomies may result in post-hepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy.
Gene Expression in the Liver Remnant Is Significantly Affected by the Size of Partial Hepatectomy: An Experimental Rat Study.
Specimen part, Treatment
View SamplesBreast cancer is a highly heterogeneous disease that is categorized into distinct tumor subtypes based on specific molecular attributes, which ultimately influence therapeutic options. Unlike ER+ and/or HER2+ cancers that are subject to specific targeted therapies, triple negative breast cancers (TNBCs) do not express these receptors, which leaves patients with limited treatment options. Thus, significant focus has been placed on identifying molecular attributes of basal-like disease that could be used to develop and/or direct novel treatment regimens. Activation of MYC signaling and inactivation of the RB-pathway are frequent events in many types of human cancers. These pathways influence many biological processes, such as cell proliferation, that contribute to the aggressiveness and therapeutic response of tumors. The current study examines the interaction of the MYC and RB pathways in mammary epithelial cell tumorigenesis.
RB loss contributes to aggressive tumor phenotypes in MYC-driven triple negative breast cancer.
Sex, Age, Specimen part
View SamplesMouse ESCs depleted of the epigenetic modifying enzyme Usp22 fail to differentiate properly. Ectopic expresison of Usp22 results in spontaneous differnetiation.
The epigenetic modifier ubiquitin-specific protease 22 (USP22) regulates embryonic stem cell differentiation via transcriptional repression of sex-determining region Y-box 2 (SOX2).
Cell line, Treatment
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