Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Gene expression analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources
PubMed2005

Gene expression analysis of cultured amniotic fluid cell with Down syndrome by DNA microarray.

Complete or partial triplication of human chromosome 21 results in Down syndrome (DS). To analyze differential gene expressions in amniotic fluid (AF) cells of DS, we used a DNA microarray system to analyze 102 genes, which included 24 genes on chromosome 21, 28 genes related to the function of brain and muscle, 36 genes related to apoptosis, 4 genes related to extracellular matrix, 8 genes related to other molecular function and 2 house-keeping genes. AF cells were collected from 12 pregnancies at 16-18 weeks of gestation in DS (n=6) and normal (n=6) subjects. Our DNA microarray experiments showed that the expressions of 11 genes were altered by at least 2-folds in DS, as follows. Ten genes, COL6A1, CASP5, AKT2, JUN, PYGM, BNIP1, OSF-2, PRSS7, COL3A1, and MBLL were down-regulated and GSTT1 was only up-regulated. The differential expressions of GSTT1 and COL3A1 were further confirmed by semi-quantitative RT-PCR for each sample. The gene dosage hypothesis on chromosome 21 may explain the neurological and other symptoms of DS. However, our results showed that only two genes (COL6A1 and PRSS7), among 24 genes on chromosome 21, were down-regulated in the AF cells of DS. Our data may provide the basis for a more systematic identification of biological markers of fetal DS, thus leading to an improved understanding of pathogenesis for fetal DS.

Amniocentesis↗
PubMed2001

Inducible IL-2 production by dendritic cells revealed by global gene expression analysis.

Dendritic cells (DCs) are strong activators of primary T cell responses. Their priming ability is acquired upon encounter with maturation stimuli. To identify the genes that are differentially expressed upon maturation induced by exposure to Gram-negative bacteria, a kinetic study of DC gene expression was done with microarrays representing 11,000 genes and ESTs (expressed sequence tags). Approximately 3000 differentially expressed transcripts were identified. We found that functional interleukin 2 (IL-2) mRNA, which gave rise to IL-2 production, was transiently up-regulated at early time-points after bacterial encounter. In contrast, macrophages did not produce IL-2 upon bacterial stimulation. Thus, IL-2 is an additional key cytokine that confers unique T cell stimulatory capacity to DCs.

Animals↗
PubMed2005

Gene expression analysis reveals a strong signature of an interferon-induced pathway in childhood lymphoblastic leukemia as well as in breast and ovarian cancer.

On the basis of epidemiological studies, infection was suggested to play a role in the etiology of human cancer. While for some cancers such a role was indeed demonstrated, there is no direct biological support for the role of viral pathogens in the pathogenesis of childhood leukemia. Using a novel bioinformatic tool that alternates between clustering and standard statistical methods of analysis, we performed a 'double-blind' search of published gene expression data of subjects with different childhood acute lymphoblastic leukemia (ALL) subtypes, looking for unanticipated partitions of patients, induced by unexpected groups of genes with correlated expression. We discovered a group of about 30 genes, related to the interferon response pathway, whose expression levels divide the ALL samples into two subgroups; high in 50, low in 285 patients. Leukemic subclasses prevalent in early childhood (the age most susceptible to infection) are over-represented in the high-expression subgroup. Similar partitions, induced by the same genes, were found also in breast and ovarian cancer but not in lung cancer, prostate cancer and lymphoma. About 40% of breast cancer samples expressed the 'interferon-related' signature. It is of interest that several studies demonstrated mouse mammary tumor virus-like sequences in about 40% of breast cancer samples. Our discovery of an unanticipated strong signature of an interferon-induced pathway provides molecular support for a role for either inflammation or viral infection in the pathogenesis of childhood leukemia as well as breast and ovarian cancer.

Base Sequence↗
PubMed2002

Gene expression analysis in microdissected renal tissue. Current challenges and strategies.

The architecture and compartmentalization of the kidney has stimulated the development of an array of microtechniques to study the functional differences between the distinct nephron segments. With the vast amounts of genomic sequence data now available, the groundwork has been laid for a comprehensive characterization of the molecular pathways defining the differences in nephron function. With the development of sensitive gene expression techniques the tools for a comprehensive molecular analysis of specific renal microenvironments have been provided: Quantitative RT-PCR technologies now allow the analysis of specific mRNAs from as little as single microdissected renal cells. A more global view of gene expression regulation is a logical development from the application of large scale profiling techniques. In this review, we will discuss the power and pitfalls of these approaches, including their potential for the functional characterization of nephron heterogeneity and diagnostic application in renal disease.

Dissection↗
PubMed2002

Gene expression analysis of human thymoma correlates with tumor stage.

Thymoma is one of the most common solid tumors in the mediastinum. The recent development of high-density oligonucleotide arrays provides a unique opportunity to generate gene expression profiles of cells from various stages of tumor progression as it occurs in actual neoplastic tissues. We used oligonucleotide arrays to monitor in vivo gene expression levels in early- (stage I or II) and late- (stage IVa) stage thymoma tissues in 36 patients. These in vivo gene expression profiles were verified by real-time quantitative RT-PCR using LightCycler. Using both methods, 2 candidate genes were identified that were more highly expressed in advanced-stage thymomas. One was a well-known gene, c-JUN, and another was an unknown gene, AL050002. AL050002 expression, but not c-JUN expression, was also correlated with the WHO classification (type B3 vs. type B1, B2 or AB). The combined use of oligonucleotide microarray and real-time RT-PCR analyses provides a powerful new approach to elucidate the in vivo molecular events correlated with tumor stage of thymoma.

DNA, Complementary↗
PubMed2000

Histone acetylation and gene expression analysis of sex lethal mutants in Drosophila.

The evolution of sex determination mechanisms is often accompanied by reduction in dosage of genes on a whole chromosome. Under these circumstances, negatively acting regulatory genes would tend to double the expression of the genome, which produces compensation of the single-sex chromosome and increases autosomal gene expression. Previous work has suggested that to reduce the autosomal expression to the female level, these dosage effects are modified by a chromatin complex specific to males, which sequesters a histone acetylase to the X. The reduced autosomal histone 4 lysine 16 (H4Lys16) acetylation results in lowered autosomal expression, while the higher acetylation on the X is mitigated by the male-specific lethal complex, preventing overexpression. In this report, we examine how mutations in the principal sex determination gene, Sex lethal (Sxl), impact the H4 acetylation and gene expression on both the X and autosomes. When Sxl expression is missing in females, we find that the sequestration occurs concordantly with reductions in autosomal H4Lys16 acetylation and gene expression on the whole. When Sxl is ectopically expressed in Sxl(M) mutant males, the sequestration is disrupted, leading to an increase in autosomal H4Lys16 acetylation and overall gene expression. In both cases we find relatively little effect upon X chromosomal gene expression.

Acetylation↗
PubMed2005

Gene-expression analysis and network discovery using Genevestigator.

The Genevestigator software suite belongs to a new generation of web-based tools that provide categorized quantitative information about elements (genes or annotations) contained in large microarray databases. The first version of Genevestigator, in use since 2004, has now been updated to enable faster, more powerful and more diverse types of queries for gene-function analysis and network discovery.

Databases, Genetic↗
PubMed2007

Hippocampal gene expression analysis using the ORESTES methodology shows that homer 1a mRNA is upregulated in the acute period of the pilocarpine epilepsy model.

In the study of temporal lobe epilepsy (TLE) the characterization of genes expressed in the hippocampus is of central importance for understanding their roles in epileptogenic mechanisms. Although several large-scale studies on TLE gene expression have been reported, precise assignment of individual genes associated with this syndrome is still debatable. Here we investigated differentially expressed genes by comparison of mRNAs from normal and epileptic rat hippocampus in the pilocarpine model of epilepsy. For this we used a powerful EST sequencing methodology, ORESTES (Open Reading frame Expressed Sequence Tags), which generates sequence datasets enriched for mRNAs open reading frames (ORFs) rather than simple 5' and 3' ends of mRNAs. Analysis of our sequences shows that ORESTES readily enables the identification of epilepsy associated ORFs. PFAM analysis of protein motifs present in our ORESTES epilepsy database revealed diverse important protein family domains, such as cytoskeletal, cell signaling and protein kinase domains, which could be involved in processes underlying epileptogenesis. More importantly, we show that the expression of homer 1a, known to be coupled to mGluR and NMDA synaptic transmission, is associated with pilocarpine induced status epilepticus (SE). The combined use of the pilocarpine model of epilepsy with the ORESTES technique can significantly contribute to the identification of specific genes and proteins related to TLE. This is the first study applying a large-scale method for rapid shotgun sequencing directed to ORFs in epilepsy research.

Animals↗
PubMed2006

Global gene expression analysis of the heat shock response in the phytopathogen Xylella fastidiosa.

Xylella fastidiosa is a phytopathogenic bacterium that is responsible for diseases in many economically important crops. Although different strains have been studied, little is known about X. fastidiosa stress responses. One of the better characterized stress responses in bacteria is the heat shock response, which induces the expression of specific genes to prevent protein misfolding and aggregation and to promote degradation of the irreversibly denatured polypeptides. To investigate X. fastidiosa genes involved in the heat shock response, we performed a whole-genome microarray analysis in a time course experiment. Globally, 261 genes were induced (9.7%) and 222 genes were repressed (8.3%). The expression profiles of the differentially expressed genes were grouped, and their expression patterns were validated by quantitative reverse transcription-PCR experiments. We determined the transcription start sites of six heat shock-inducible genes and analyzed their promoter regions, which allowed us to propose a putative consensus for sigma(32) promoters in Xylella and to suggest additional genes as putative members of this regulon. Besides the induction of classical heat shock protein genes, we observed the up-regulation of virulence-associated genes such as vapD and of genes for hemagglutinins, hemolysin, and xylan-degrading enzymes, which may indicate the importance of heat stress to bacterial pathogenesis. In addition, we observed the repression of genes related to fimbriae, aerobic respiration, and protein biosynthesis and the induction of genes related to the extracytoplasmic stress response and some phage-related genes, revealing the complex network of genes that work together in response to heat shock.

Endopeptidases↗
PubMed2024

Multi-organ gene expression analysis and network modeling reveal regulatory control cascades during the development of hypertension in female spontaneously hypertensive rat.

Hypertension is a multifactorial disease with stage-specific gene expression changes occurring in multiple organs over time. The temporal sequence and the extent of gene regulatory network changes occurring across organs during the development of hypertension remain unresolved. In this study, female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were used to analyze expression patterns of 96 genes spanning inflammatory, metabolic, sympathetic, fibrotic, and renin-angiotensin (RAS) pathways in five organs, at five time points from the onset to established hypertension. We analyzed this multi-dimensional dataset containing ~15,000 data points and developed a data-driven dynamic network model that accounts for gene regulatory influences within and across visceral organs and multiple brainstem autonomic control regions. We integrated the data from female SHR and WKY with published multiorgan gene expression data from male SHR and WKY. In female SHR, catecholaminergic processes in the adrenal gland showed the earliest gene expression changes prior to inflammation-related gene expression changes in the kidney and liver. Hypertension pathogenesis in male SHR instead manifested early as catecholaminergic gene expression changes in brainstem and kidney, followed by an upregulation of inflammation-related genes in liver. RAS-related gene expression from the kidney-liver-lung axis was downregulated and intra-adrenal RAS was upregulated in female SHR, whereas the opposite pattern of gene regulation was observed in male SHR. We identified disease-specific and sex-specific differences in regulatory interactions within and across organs. The inferred multi-organ network model suggests a diminished influence of central autonomic neural circuits over multi-organ gene expression changes in female SHR. Our results point to the gene regulatory influence of the adrenal gland on spleen in female SHR, as compared to brainstem influence on kidney in male SHR. Our integrated molecular profiling and network modeling identified a stage-specific, sex-dependent, multi-organ cascade of gene regulation during the development of hypertension.

Animals↗
PubMed1986

Regulation of class II gene expression: analysis in B cell stimulatory factor 1-inducible murine pre-B cell lines.

We have analyzed the mechanism of action of BSF-1 on class II gene expression in two murine pre-B cell lines that are at different stages of differentiation. In vitro transcription assays demonstrated that BSF-1 induced rapid transcription of class II genes within 1 hr by a mechanism that was independent of protein synthesis. Although cell surface expression of class II was detectable by 2 hr after induction and persisted for up to 96 hr after removal of BSF-1, levels of class II-specific mRNA and density of cell surface class II increased to a maximum between 24 and 72 hr after induction. Furthermore, prostaglandin E2 prevented the induction of class II gene expression by BSF-1. The effects of BSF-1 are unlikely to be mediated through calcium fluxes or activation of protein kinase C, since treatment with agents such as PMA and the calcium ionophore A23187 did not result in expression of class II molecules. Other lymphokines, such as IFN-gamma, IL 1, IL 2, and IL 3, did not affect class II gene expression in these two cell lines. These data provide further insight into the mechanisms by which class II gene expression is regulated in B cells.

Animals↗
PubMed2000

The application of DNA microarrays in gene expression analysis.

DNA microarray technology is a new and powerful technology that will substantially increase the speed of molecular biological research. This paper gives a survey of DNA microarray technology and its use in gene expression studies. The technical aspects and their potential improvements are discussed. These comprise array manufacturing and design, array hybridisation, scanning, and data handling. Furthermore, it is discussed how DNA microarrays can be applied in the working fields of: safety, functionality and health of food and gene discovery and pathway engineering in plants.

Biotechnology↗
PubMed2004

Global gene expression analysis of rat colon cancers induced by a food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Colon cancers develop after accumulation of multiple genetic and epigenetic alterations in colon epithelial cells. To shed light on global changes in gene expression of colon cancers and to gain further insight into the molecular mechanisms underlying colon carcinogenesis, we have conducted a comprehensive microarray analysis of mRNA using a rat colon cancer model with the food-borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Of 8749 genes or ESTs on a high density oligonucleotide microarray, 27 and 46 were over- and underexpressed, respectively, by > or =3-fold in colon cancers in common in two rat strains with distinct susceptibility to PhIP carcinogenesis. For example, genes involved in inflammation and matrix proteases and a cell cycle regulator gene, cyclin D2, were highly expressed in colon cancers. In contrast, genes encoding structural proteins, muscle-related proteins, matrix-composing and mucin-like proteins were underexpressed. Interestingly, a subset of genes whose expression is characteristic of Paneth cells, i.e. the defensins and matrilysin, were highly overexpressed in colon cancers. The presence of defensin 3 and defensin 5 transcripts in cancer cells could also be confirmed by in situ mRNA hybridization. Furthermore, Alcian blue/periodic acid Schiff base (AB-PAS) staining and immunohistochemical analysis with an anti-lysozyme antibody demonstrated Paneth cells in the cancer tissues. AB-PAS-positive cells were also observed in high grade dysplastic aberrant crypt foci, which are considered to be preneoplastic lesions of the colon. Our results suggest that Paneth cell differentiation in colon epithelial cells could be an early morphological change in cryptic cells during colon carcinogenesis.

Alcian Blue↗
PubMed2004

A neurogenomics approach to gene expression analysis in the developing brain.

Secreted and transmembrane proteins provide critical functions in the signaling networks essential for neurogenesis. We used a genetic signal sequence gene trap approach to isolate 189 genes expressed during development in e16.5 whole head, e16.5 hippocampus and e14.5 cerebellum. Gene ontology programs were used to classify the genes into respective biological processes. Four major classes of biological processes known to be important during development were identified: cell communication, cell physiology processes, metabolism and morphogenesis. We used in situ hybridization to determine the temporal and spatial patterns of gene expression in the developing brain using this set of probes. The results demonstrate that gene expression patterns can highlight potential gene functions in specific brain regions. We propose that combining bioinformatics with the gene expression pattern is an effective strategy to identify genes that may play critical roles during brain development.

Animals↗
PubMed1991

Baculovirus gp64 gene expression: analysis of sequences modulating early transcription and transactivation by IE1.

Expression of the baculovirus major envelope glycoprotein gene (gp64) is regulated by transcription from both early and late promoters. To characterize the early promoter and identify sequences involved in the regulation of gp64 early transcription, promoter-reporter gene fusions were generated from the Orygia pseudotsugata nuclear polyhedrosis virus gp64 promoter and were analyzed by transient expression in uninfected insect cells. For these analyses, 5' deletion mutations were constructed in the gp64 upstream regulatory region. Larger promoter constructs were functional in uninfected Lymantria dispar cells, indicating that transcription from the gp64 early promoter required no additional viral gene products. Deletion analysis of the gp64 upstream region revealed several regulatory regions. These included a putative negative regulatory element between -319 and -166 nucleotides (nt) and multiple positive regulatory elements between -166 and -77 nt. Deletion of the TATA box located between -77 and -62 nt resulted in the loss of transcriptional activity. Cotransfections of reporter constructs and a plasmid containing a baculovirus transcriptional transactivator gene (Autographa californica nuclear polyhedrosis virus IE1) resulted in transcriptional transactivation of all constructs containing an intact TATA box. These data demonstrate that sequences upstream of the gp64 TATA box are not essential for IE1 transactivation and that only 34 nt upstream of the early transcription start site were necessary for basal levels of transcription and for transactivation by IE1. Function of the gp64 early promoter was also examined in cell lines from Spodoptera frugiperda and Drosophila melanogaster.

Amino Acid Sequence↗
PubMed2004

Gene expression analysis reveals evidence for inactivation of the TGF-beta signaling cascade in autonomously functioning thyroid nodules.

Molecular events that lead to the development of autonomously functioning thyroid nodules (AFTNs) are somatic mutations of the thyrotropin receptor (TSHR) in approximately 60% of the nodules and less frequently, somatic mutations in the Gsalpha protein. However, AFTNs without known mutations indicate that other causes remain to be identified. Moreover, the impact of constitutively activating TSHR mutations on the signal transduction network of the thyroid epithelial cell is unknown. We therefore investigated gene expression in 15 AFTNs and their surrounding tissue using Affymetrix GeneChips. Most prominently, data analysis revealed a changed pattern of gene expression in the TGF-beta signaling cascade and 25 differentially regulated genes in AFTNs, including thyroid peroxidase, type I iodothyronine deiodinase and sialyltransferase (SIAT) 1. Strikingly coexpression of SIAT 1 and TSHR in COS-7 cells increased TSH binding and cell surface expression of the TSHR. Moreover, differences in gene expression patterns for AFTNs with and without TSHR mutations indicate specific alterations of signal transduction in AFTNs without TSHR mutations. These results suggest that AFTNs with TSHR mutations harbor further mechanisms of forward stimulation. Furthermore, they give important leads to elucidate the molecular etiology of AFTNs without TSHR mutations.

Animals↗