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Results for “Genomic profiling”

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At least 883 records · Page 49Linked to original sources
PubMed2005

Replication-associated strand asymmetries in mammalian genomes: toward detection of replication origins.

In the course of evolution, mutations do not affect both strands of genomic DNA equally. This imbalance mainly results from asymmetric DNA mutation and repair processes associated with replication and transcription. In prokaryotes, prevalence of G over C and T over A is frequently observed in the leading strand. The sign of the resulting TA and GC skews changes abruptly when crossing replication-origin and termination sites, producing characteristic step-like transitions. In mammals, transcription-coupled skews have been detected, but so far, no bias has been associated with replication. Here, analysis of intergenic and transcribed regions flanking experimentally identified human replication origins and the corresponding mouse and dog homologous regions demonstrates the existence of compositional strand asymmetries associated with replication. Multiscale analysis of human genome skew profiles reveals numerous transitions that allow us to identify a set of 1,000 putative replication initiation zones. Around these putative origins, the skew profile displays a characteristic jagged pattern also observed in mouse and dog genomes. We therefore propose that in mammalian cells, replication termination sites are randomly distributed between adjacent origins. Taken together, these analyses constitute a step toward genome-wide studies of replication mechanisms.

Animals↗
PubMedDate not supplied

Future directions in cancer research: impact of the completion of the human genome.

The sequencing of the human genome will have a major impact on the prevention, diagnosis, treatment, monitoring, and outcome of cancer. Progress will most likely occur in a stepwise fashion with the biggest initial impact in diagnosis and molecular targeting of new medicines. Advances in genomics and proteomics have already resulted in major findings that are facilitating earlier cancer diagnosis and disease stratification. New treatments that target specific pathways are well underway for many cancers and likewise, molecular analyses aimed at finding medicines with reduced toxicities are being conducted. Close interaction with the Food and Drug Administration will be very important to integrate these new technologies into product development and the approval of new medicines and diagnostics. Clearly, we are now approaching the era of personalized medicines in which one has the opportunity to maximize the efficacy and minimize the side effects of the cancer treatments. The ability to translate this new technology into improving cancer patient care and outcomes will require that scientists from academia, industry, and govemment work together closely to develop the framework and standards necessary to maximize the benefit of the human genome project.

Forecasting↗
PubMed2026

Comparative genomics reveals lineage-associated structural variation and diversification in a barley fungal pathogen.

Leaf rust, caused by Puccinia hordei, is a major barley disease worldwide. Despite repeated shifts in virulence, contrasting reproductive histories, and emerging fungicide insensitivity, the genomic basis of its diversification and adaptation remains poorly understood. In this study, we generated haplotype-resolved, chromosome-level genome assemblies for two isolates with contrasting virulence and analyzed 41 Australian isolates collected over 54 yr (1966-2020), integrating comparative and population genomics, mating-type gene phylogenies, chromosome-specific k-mer profiling, genome-wide copy-number variation (CNV) analysis, and gene-expression analysis. We identified a structurally dynamic chromosome characterized by repeat-associated rearrangements, structural variation, and lineage-associated CNV, representing the first evidence in a rust fungus of chromosome-scale structural diversification of this extent. Population analyses distinguished clonally expanded lineages from recombination-associated lineages, with mating-type gene phylogenies providing further support for lineage differentiation. More recently collected isolates showed increased duplication-associated variation, and CNV boundaries were associated with structural-variant breakpoints. We also identified lineage-associated amplification of Cyp51, with increased copy number associated with higher transcript abundance, supporting a potential role in fungicide adaptation. Overall, our findings highlight structural variation, contrasting reproductive histories, and lineage-associated CNV as important contributors to diversification in P. hordei, providing insights for future rust pathogen surveillance and management strategies.

Cyp51 gene↗
PubMed2006

TFIIA plays a role in the response to oxidative stress.

To characterize the role of the general transcription factor TFIIA in the regulation of gene expression by RNA polymerase II, we examined the transcriptional profiles of TFIIA mutants of Saccharomyces cerevisiae using DNA microarrays. Whole-genome expression profiles were determined for three different mutants with mutations in the gene coding for the small subunit of TFIIA, TOA2. Depending on the particular mutant strain, approximately 11 to 27% of the expressed genes exhibit altered message levels. A search for common motifs in the upstream regions of the pool of genes decreased in all three mutants yielded the binding site for Yap1, the transcription factor that regulates the response to oxidative stress. Consistent with a TFIIA-Yap1 connection, the TFIIA mutants are unable to grow under conditions that require the oxidative stress response. Underexpression of Yap1-regulated genes in the TFIIA mutant strains is not the result of decreased expression of Yap1 protein, since immunoblot analysis indicates similar amounts of Yap1 in the wild-type and mutant strains. In addition, intracellular localization studies indicate that both the wild-type and mutant strains localize Yap1 indistinguishably in response to oxidative stress. As such, the decrease in transcription of Yap1-dependent genes in the TFIIA mutant strains appears to reflect a compromised interaction between Yap1 and TFIIA. This hypothesis is supported by the observations that Yap1 and TFIIA interact both in vivo and in vitro. Taken together, these studies demonstrate a dependence of Yap1 on TFIIA function and highlight a new role for TFIIA in the cellular mechanism of defense against reactive oxygen species.

Amino Acid Sequence↗
PubMed2001

[Perspectives on postgenome medicine: Cancer].

Carcinogenesis is a multistep process which is the outcome of the accumulation of genetic and epigenetic events. However, characteristics of cancers, such as drug sensitivity, abilities in invasion and metastasis, are different in each patients, and reliable prediction of those characteristics is not available. DNA microarray and SNP have become the most widely used functional genomics tools. Microarray technology has provided the ability to analyse the expression profiles for thousands of genes, and a wealth of new information that should aid in cancer diagnosis and ultimately in therapy. The SNP project also will generate very variable resources for cancer therapy. The medicine in the next century will be so called 'personalized medicine' based on the new information of patients and diseases.

Gene Expression Profiling↗
PubMed2005

Characterization of gene expression profiles of T cells during anti-tumor response.

BACKGROUND AND AIMS: T cells of tumor-bearing mice or cancer patients exhibit an immune dysfunction, enabling the tumor to escape immune surveillance. METHODS: The experiments are based on EL4 thymoma cells that were transfected with costimulatory ligands B7-1, B7-2, or both at the same time. We used oligonucleotide-based DNA chip microarrays to characterize the genomic expression profile of peripheral T cells according to their anti-tumor immune response in vivo. These murine T cells were also characterized by ELISA, FACS analysis, and co-stimulatory assays. RESULTS: Using commonly established methods, such as FACS analysis or the analysis of the cytokine profile by ELISA, it was not possible to determine functional differences in the in vivo activity of T lymphocytes against tumor cells. EL4 tumor cells induced multiple anti-tumor immune responses in vivo depending on their B7 expression. We successfully used microarray analysis to identify genes that were differentially expressed in the dysfunctional T cells, which were unable to reject tumors in vivo. Although Th1 and Th2 cytokine expression was not affected, we observed differential expression of genes involved in the regulation of an innate immune response. CONCLUSION: Our results provide evidence that the anti-tumor response can be identified by the "gene profile" of T cells. Genomic scale analysis offers the opportunity to identify subtle changes in gene expression in T cells reflecting a distinct biological behavior in vivo.

Animals↗
PubMed2006

Profiling signalling pathways of the receptor activator of NF-kappaB ligand-induced osteoclast formation in mouse monocyte cells, RAW264.7.

Cell-based signal chemical genomics can profile the signalling pathway for certain cellular events by using a target-known chemical library. To ascertain its usefulness, the receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis in mouse monocyte/macrophage cells RAW264.7 was used as an in vitro experimental model. Of 180 target-known inhibitors/activators formatted in a 384-well plate, 8 chemicals were shown to inhibit the osteoclast formation, but 4 chemicals enhanced this process. A variety of references support, or possibly lead one to expect the effects of these 12 chemicals on the cellular process of osteoclastogenesis in RAW264.7 cells, but several signalling pathways were newly found in this study; for example, CA-074 Me inhibiting cathepsin B and nitrendipine blocking the calcium channel could have the potential to inhibit the osteoclast formation as well as bone resorption. This is a simple but very fast and powerful method of profiling the signalling pathway of certain cellular events. Signal chemical genomics could provide invaluable information for the exploration of new target signalling processes and further target-based drug discovery strategies.

Acid Phosphatase↗
PubMed2003

Ozone-induced disruptions of lung transcriptomes.

We have analyzed changes in approximately 4000 lung mRNAs, with GeneChips, in mice exposed to 1 ppm O(3) for three consecutive nights (8 h per night). Differential gene expression analysis identified approximately 260 O(3) sensitive genes; approximately 80% of these were repressed and approximately 20% were induced in O(3)-exposed mice compared to the air-exposed controls. A 20-fold induction of serum amyloid A3 mRNA by O(3) suggested activation of NF-kappaB and CCAAT/enhancer binding protein-mediated pathways by inflammatory cytokines. Induction (up to 14-fold) of 12 genes that increase DNA synthesis and cell cycle progression, and increase (approximately 7-fold) in CD44 mRNA and macrophage metalloelastase suggested a state of O(3)-induced hyperplasia and lung remodeling. Several mRNAs encoding enzymes of xenobiotic metabolism and cytoskeletal functions were repressed and may suggest cytokine mediated suppression of cytochrome P450 expression and cachexia-like inflammatory state in ozone-exposed lungs. The expressions of approximately 30 genes of immune response were also repressed. Collectively this genome-wide analysis of lungs identified ozone-induced disruption of gene transcriptional profile indicative of increased cellular proliferation under suppressed immune surveillance and xenobiotic metabolism.

Air↗
PubMed1996

Pulsed-field gel electrophoresis indicates genotypic heterogeneity among Campylobacter upsaliensis strains.

To determine the genomic relatedness among a selection of animal and human Campylobacter upsaliensis isolates, macrorestriction profiles were generated for 20 C. upsaliensis strains, among 7 serogroups, using pulsed-field gel electrophoresis (PFGE). XhoI, SalI and SacII restriction enzyme profiles indicated genomic heterogeneity among strains. Using XhoI and SacII restriction enzyme digestion, genomic similarities between some pairs of strains were Lior serogroup specific. The genomic sizes of these isolates varied from 1.74 to 2.09 Mb. These results demonstrate molecular heterogeneity of this species similar to that found among Helicobacter pylori isolates. Among C. upsaliensis strains, PFGE is highly discriminatory and should prove a useful molecular typing method for epidemiological purposes.

Animals↗
PubMed2006

Large-scale analysis of neural stem cells and progenitor cells.

The past few years have seen remarkable progress in our understanding of stem cell biology. The wealth of genomic data and the multiplicity of sources have enabled researchers to begin to profile stem cells in detail. In this paper we describe the biological and technical controls necessary to obtain reliable data and the relative merits of various large-scale analytical techniques including microarray, expressed sequence tag enumeration, serial analysis of gene expression and massively parallel signature sequencing. We suggest that while much has been learned, additional information remains to be gleaned by meta-analysis of existing data.

Animals↗
PubMed2001

Chemical genomics: what will it take and who gets to play?

Chemical genomics requires continued advances in combinatorial chemistry, protein biochemistry, miniaturization, automation, and global profiling technology. Although innovation in each of these areas can come from individual academic labs, it will require large, well-funded centers to integrate these components and freely distribute both data and reagents.

Automation↗
PubMed2003

MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma.

The MALT1 gene was identified through its involvement in t(11;18)(q21;q21), seen in 30% of cases of mucosa-associated lymphoid tissue (MALT) lymphoma. Here, we show that deregulated MALT1 expression may occur in B-cell non-Hodgkin lymphoma (B-NHL) of various histologic subtypes either through translocation to the immunoglobulin heavy chain (IGH) locus or by genomic amplification. First, 2 cases, one case of MALT lymphoma and another of aggressive marginal zone lymphoma (MZL) with t(14;18)(q32;q21), cytogenetically identical to the translocation involving BCL2, were shown by fluorescence in situ hybridization (FISH) to involve MALT1, which lies about 5 Mb centromeric of BCL2. Molecular cloning of both by long-distance inverse polymerase chain reaction showed breakpoints lying 1 to 2 kilobase (kb) centromeric of the first 5' MALT1 exon; both cases showed MALT1 overexpression at either RNA or protein levels. Second, we examined the structure and gene expression profile of genomic amplifications involving 18q21 in a panel of 40 B-NHL cell lines using comparative genomic hybridization to microarrays (array CGH) and gene expression profiling techniques. Using array CGH, 2 peaks of genomic amplification were observed, one centered around BCL2 and the other around MALT1. Ofthe 3 cell lines with MALT1 amplification, 2 showed MALT1 overexpression as assessed by gene profiling, quantitative reverse transcription-polymerase chain reaction (QRT-PCR), and Western blotting. To determine if comparable events occurred in primary MALT and splenic MZL tumors, 40 cases were analyzed by FISH or QRT-PCR; genomic amplification and MALT1 overexpression were seen in 2 cases. Together, these data implicate MALT1 as a dominant oncogene that may play a role in the pathogenesis of B-NHL.

Aged↗
PubMed1993

Demonstration that 1 beta,25-dihydroxyvitamin D3 is an antagonist of the nongenomic but not genomic biological responses and biological profile of the three A-ring diastereomers of 1 alpha,25-dihydroxyvitamin D3.

The steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) generates biological responses via both genomic and nongenomic mechanisms. This article reports the biological profile of four A-ring diastereomers of this secosteroid (results are expressed as percentage of the response of 1 alpha,25-(OH)2D3. The activity of the compounds, 1 alpha,25-(OH)2D3, 1 alpha,25-(OH)2-3-epivitamin D3, 1 beta,25-(OH)2D3, 1 beta,25-(OH)2-3-epivitamin D3, for in vivo intestinal Ca2+ absorption and bone Ca2+ mobilization and in vitro binding to the nuclear receptor (genomic responses) was, respectively, 100, 2.8, < 0.1, and < 0.1% (intestinal Ca2+ absorption); 100, 1.5, < 0.1, and < 0.1% (bone Ca2+ mobilization); 100, 24, 0.2, and 0.8% (receptor binding). In the in vivo nongenomic transcaltachia assay the results were 100, 80, 0, and 20-30%, and in ROS 17/2.8 cells (45Ca2+ uptake through voltage-gated Ca2+ channels) 1 alpha,25-(OH)2D3 had 100% activity and 1 beta,25-(OH)2D3 (the only diastereomer evaluated) had no agonist activity. Keratinocyte proliferation was inhibited in the order 1 alpha,25-(OH)2D3 > 1 alpha,25-(OH)2-3-epivitamin D3 > 1 beta,25-(OH)2D3 > 1 beta,25-(OH)2-3-epivitamin D3. 1 beta,25-(OH)2D3 was a potent antagonist of 1 alpha,25-(OH)2D3-mediated transcaltachia and 45Ca2+ uptake in ROS 17/2.8 cells but was unable to block the genomic 1 alpha,25-(OH)2D3 induction of chick calbindin-D28k (in vivo), induction of MG-63 cell osteocalcin, and HL-60 cell differentiation. These results suggest that analogs of 1 alpha,25-(OH)2D3 may be synthesized which are selective agonists or antagonists of genomic or nongenomic responses in the vitamin D endocrine system.

Animals↗