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At least 757 records · Page 42Linked to original sources
PubMed2002

Genomic analysis using conditional phenotypes generated by antisense RNA.

Antisense technology has been widely used to regulate gene expression. A tetracycline (tet)-regulated antisense-RNA-expressing system has been developed and used to downregulate chromosomally derived genes expressed in Staphylococcus aureus. This downregulation subsequently provides an evaluation of the virulence factor and drug targets. The regulated antisense RNA library allows for genome-wide analyses of the functions of staphylococcal gene products for growth in culture and survival during infection. Moreover, this antisense RNA technology may provide a key tool to identify mechanisms of novel antibacterial compound action.

Drug Resistance, Bacterial↗
PubMed2002

Genomic analysis of protein kinases, protein phosphatases and two-component regulatory systems of the cyanobacterium Anabaena sp. strain PCC 7120.

Anabaena sp. PCC 7120 is a cyanobacterium capable of performing several important biological functions: photosynthesis, nitrogen fixation, cell differentiation, cell-cell communication, etc. These activities require an extensive signaling capability in order to respond to the changing environment. Based on the genomic data, we have retrieved several gene families encoding signaling components. It is estimated that 211 genes encode two-component signaling elements, and 66 genes encode Ser/Thr kinases and phosphatases. These genes together represent 4.2% of the coding capacity of the whole genome, making Anabaena PCC 7120 a leading member among prokaryotes in terms of its signaling potential. It is known that two-component systems are composed of a few basic modules that can arrange into different structures best adapted for each signaling system. Many proteins in Anabaena PCC 7120 have incorporated both modules of two-component systems and catalytic domains of either Ser/Thr kinases or phosphatases. A family of 13 genes encode proteins with both a Ser/Thr kinase domain and a His kinase domain, and another four genes were also found whose products have both a response regulator domain and a Ser/Thr phosphatase domain. Of all the signaling proteins in Anabaena PCC 7120, about one third (35%) are conserved in the genome of the unicellular cyanobacterium strain Synechocystis sp. PCC 6803. Interestingly, one subfamily of His kinases and two subfamilies of response regulators are found in Anabaena PCC 7120 but are absent in Synechocystis PCC 6803. This study constitutes a basis for analyses of signal transduction in Anabaena PCC 7120 using functional genomic approaches.

Anabaena↗
PubMed2003

Whole-genome analysis of two-component signal transduction genes in fungal pathogens.

Two-component phosphorelay systems are minimally comprised of a histidine kinase (HK) component, which autophosphorylates in response to an environmental stimulus, and a response regulator (RR) component, which transmits the signal, resulting in an output such as activation of transcription, or of a mitogen-activated protein kinase cascade. The genomes of the yeasts Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Candida albicans encode one, three, and three HKs, respectively. In contrast, the genome sequences of the filamentous ascomycetes Neurospora crassa, Cochliobolus heterostrophus (Bipolaris maydis), Gibberella moniliformis (Fusarium verticillioides), and Botryotinia fuckeliana (Botrytis cinerea) encode an extensive family of two-component signaling proteins. The putative HKs fall into 11 classes. Most of these classes are represented in each filamentous ascomycete species examined. A few of these classes are significantly more prevalent in the fungal pathogens than in the saprobe N. crassa, suggesting that these groups contain paralogs required for virulence. Despite the larger numbers of HKs in filamentous ascomycetes than in yeasts, all of the ascomycetes contain virtually the same downstream histidine phosphotransfer proteins and RR proteins, suggesting extensive cross talk or redundancy among HKs.

Amino Acid Sequence↗
PubMed2006

LegumeDB1 bioinformatics resource: comparative genomic analysis and novel cross-genera marker identification in lupin and pasture legume species.

The identification of markers in legume pasture crops, which can be associated with traits such as protein and lipid production, disease resistance, and reduced pod shattering, is generally accepted as an important strategy for improving the agronomic performance of these crops. It has been demonstrated that many quantitative trait loci (QTLs) identified in one species can be found in other plant species. Detailed legume comparative genomic analyses can characterize the genome organization between model legume species (e.g., Medicago truncatula, Lotus japonicus) and economically important crops such as soybean (Glycine max), pea (Pisum sativum), chickpea (Cicer arietinum), and lupin (Lupinus angustifolius), thereby identifying candidate gene markers that can be used to track QTLs in lupin and pasture legume breeding. LegumeDB is a Web-based bioinformatics resource for legume researchers. LegumeDB analysis of Medicago truncatula expressed sequence tags (ESTs) has identified novel simple sequence repeat (SSR) markers (16 tested), some of which have been putatively linked to symbiosome membrane proteins in root nodules and cell-wall proteins important in plant-pathogen defence mechanisms. These novel markers by preliminary PCR assays have been detected in Medicago truncatula and detected in at least one other legume species, Lotus japonicus, Glycine max, Cicer arietinum, and (or) Lupinus angustifolius (15/16 tested). Ongoing research has validated some of these markers to map them in a range of legume species that can then be used to compile composite genetic and physical maps. In this paper, we outline the features and capabilities of LegumeDB as an interactive application that provides legume genetic and physical comparative maps, and the efficient feature identification and annotation of the vast tracks of model legume sequences for convenient data integration and visualization. LegumeDB has been used to identify potential novel cross-genera polymorphic legume markers that map to agronomic traits, supporting the accelerated identification of molecular genetic factors underpinning important agronomic attributes in lupin.

Chromosome Mapping↗
PubMed2006

Wide genomic analysis of human endometrial receptivity: new times, new opportunities.

Microarray technology has broadened the insight into many research fields allowing scientists to analyse the expression of many genes in quick and efficient experiments aimed at translating these findings into clinical applications. In reproductive medicine, researchers have exploited microarrays to increase understanding of the molecular mechanisms involved in endometrial receptivity and how a possible therapeutic translation can be feasible. In the last 4 years, several studies have focused on the genomics of the human endometrium in different physiological and pathological conditions, and these studies have generated a large amount of information about the regulation and dysregulation of the window of implantation (WOI) genes in fertile, subfertile and refractory conditions. However, the key molecules/mechanisms in endometrial receptivity remain to be elucidated. In this comprehensive review, we have analysed the available results obtained in our own and other laboratories, defining the genomic profile of the receptive endometrium in different situations and its possible clinical application.

Animals↗
PubMed2003

Genomic analysis of glucocorticoid-regulated promoters in murine T-lymphoma cells.

We have undertaken a high-throughput analysis to identify targets of glucocorticoid regulation in P1798 murine T-lymphoma cells. G1/S-arrested cultures were treated for 8 hours with 0.1 microM dexamethasone (dex) in the presence and absence of 1 microg/ml cycloheximide. Untreated cultures and cultures exposed to cycloheximide alone were prepared as controls. RNA was isolated and gene expression analyzed using Affymetrix MG-U74A oligonucleotide arrays (Gene Chips). Three independent experiments were performed. The data were analyzed using a variety of statistical and analytical approaches in order to identify primary transcriptional targets of the glucocorticoid receptor. We identified 44 genes that increase by > 2-fold in both dex-treated and dex + cycloheximide-treated cultures (relative to control and cycloheximide-treated cultures) in three replicate experiments. Statistical analysis of control data indicate that the probability that a given probeset would, as a result of random error, increase > 2-fold both in the presence and absence of cycloheximide in two independent experiments is approximately 7 x 10(-9). We have retrieved from the Celera mouse genomic sequence 8 kb of promoter sequence, spanning 4 kb either side of the 5'-end of the cDNA from eight of the induced genes. These sequences were analyzed for potential glucocorticoid receptor binding sites. Five of these genes contain the sequence ACAnnnTGTnCT within 4 kb of the presumptive transcriptional start site. Eight control genes were selected at random and analyzed for the sequence ACAnnnTGTnCT. Two control genes had such sequences within 4 kb of the transcriptional start site.

Animals↗
PubMed2005

Genomic analysis of early murine mammary gland development using novel probe-level algorithms.

We describe a novel algorithm (ChipStat) for detecting gene-expression changes utilizing probe-level comparisons of replicate Affymetrix oligonucleotide microarray data. A combined detection approach is shown to yield greater sensitivity than a number of widely used methodologies including SAM, dChip and logit-T. Using this approach, we identify alterations in functional pathways during murine neonatal-pubertal mammary development that include the coordinate upregulation of major urinary proteins and the downregulation of loci exhibiting reciprocal imprinting.

Algorithms↗
PubMed2005

Genomic analysis of five chromosome 7p deletion patients with Greig cephalopolysyndactyly syndrome (GCPS).

Chromosomal deletions on chromosome 7p are associated with Greig cephalopolysyndactyly syndrome (GCPS, OMIM 175700) a syndrome affecting the development of the skull, face, and limbs. We have compared data from molecular cytogenetic and genetic analyses with clinical symptoms from five previously published GCPS deletion patients, including a pair of monozygotic twins. The genomic DNA of the probands and their parents, as well as the DNA from monoallelic cell lines of two patients, was analyzed using microsatellite markers. In some cases (e.g. where the microsatellite studies were uninformative) we also used fluorescence in situ hybridization (FISH) with bacterial artificial chromosomes (BAC) probes. The fine mapping results of the deletions and genomic data from chromosome 7, were compared to the clinical symptoms. Common breakpoint sequences or mutation hotspots were not observed. Mutation screening for PGAM2, which is responsible for a form of myopathy with recessive inheritance, was performed in all patients. Loss of heterozygosity for known genes with dominant inheritance, such as the glucokinase gene (GCK), which, when mutated or haploinsufficient, is responsible for maturity-onset diabetes of the young, type II (MODY2, OMIM 125851), was identified and included in a genetic counseling of the patients' families.

Abnormalities, Multiple↗
PubMed2006

Genomic analysis of pilocytic astrocytomas at 0.97 Mb resolution shows an increasing tendency toward chromosomal copy number change with age.

Brain tumors are the most common solid tumors of childhood, accounting for over 20% of cancers in children under 15 years of age. Pilocytic astrocytomas (PAs), World Health Organization grade I, are one of the most frequently occurring childhood brain tumors, yet little is known about genetic changes characterizing this entity. We have used microarray comparative genomic hybridization at 0.97 Mb resolution to study a series of PAs (n = 44). No copy number abnormality was seen in 64% of cases at this resolution. However, whole chromosomal gain (median 5 chromosomes affected) occurred in 32% of tumors. The most frequently affected chromosomes were 5 and 7 (11 of 44 cases each) followed by 6, 11, 15, and 20 (greater than 10% of cases each). Findings were confirmed by fluorescence in situ hybridization and microsatellite analysis in a subset of tumors. Chromosomal gain was significantly more frequent in PAs from patients over 15 years old (p = 0.03, Fisher exact test). The number of chromosomes involved was also significantly greater in the older group (p = 0.02, Mann-Whitney U test). One case (2%) showed a region of gain on chromosome 3 and one (2%) a deletion on 6q as their sole abnormalities. This is the first genomewide study to show this nonrandom pattern of genetic alteration in pilocytic astrocytomas.

Adolescent↗
PubMed1997

Genome analysis in Neurospora crassa; cloning of four loci arginine-1 (arg-1), methionine-6 (met-6), unknown-7 (un-7), and ribosome production-1 (rip-1) and associated chromosome walking.

We have cloned four Neurospora crassa genes by complementation analysis. Cloned genes include the arginine-1 (arg-1), methionine-6 (met-6), unknown-7 (un-7), and ribosome production-1 (rip-1) loci. Chromosome walks were initiated in ordered cosmid libraries from the cloned loci. A total of about 700 kb of the Neurospora genome is covered in these walks.

Arginine↗
PubMed2006

In silico genomic analysis of the human and murine guanylate-binding protein (GBP) gene clusters.

The guanylate-binding proteins (GBPs) were among the first interferon (IFN)-stimulated genes (ISGs) discovered, but until recently, little was known about their functions and even less about the composition of the gene family. Analysis of the promoter of human GBP-1 contributed significantly toward the understanding of Jak-Stat signaling and the delineation of the IFN-gamma activation site (GAS) and IFN-stimulated response element (ISRE) promoter elements. In this study, we have examined the genomic arrangement and composition of the GBPs in both mouse and humans. There are seven GBP paralogs in humans and at least one pseudogene, all of which are located in a cluster of genes on chromosome 1. Five of the six MuGBPs and a GBP pseudogene are clustered in a syntenic region on chromosome 3. The sixth MuGBP, MuGBP-4, and three GBP pseudogenes are located on chromosome 5. As might be expected, the GBPs share similar genomic organizations of introns and exons. Five of the MuGBPs had previously been shown to be coordinately induced by IFNs, and as expected, all of the MuGBPs have GAS and ISRE elements in their promoters. Interestingly, not all of the HuGBPs have GAS and ISRE elements, suggesting that not all GBPs are IFN responsive in humans.

Amino Acid Sequence↗
PubMed1998

Highly specific protein sequence motifs for genome analysis.

We present a method for discovering conserved sequence motifs from families of aligned protein sequences. The method has been implemented as a computer program called EMOTIF (http://motif. stanford.edu/emotif). Given an aligned set of protein sequences, EMOTIF generates a set of motifs with a wide range of specificities and sensitivities. EMOTIF also can generate motifs that describe possible subfamilies of a protein superfamily. A disjunction of such motifs often can represent the entire superfamily with high specificity and sensitivity. We have used EMOTIF to generate sets of motifs from all 7,000 protein alignments in the BLOCKS and PRINTS databases. The resulting database, called IDENTIFY (http://motif. stanford.edu/identify), contains more than 50,000 motifs. For each alignment, the database contains several motifs having a probability of matching a false positive that range from 10(-10) to 10(-5). Highly specific motifs are well suited for searching entire proteomes, while generating very few false predictions. IDENTIFY assigns biological functions to 25-30% of all proteins encoded by the Saccharomyces cerevisiae genome and by several bacterial genomes. In particular, IDENTIFY assigned functions to 172 of proteins of unknown function in the yeast genome.

Amino Acid Sequence↗
PubMed2003

Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae.

We have used a single-gene deletion mutant bank to identify the genes required for meiosis and sporulation among 4323 nonessential Saccharomyces cerevisiae annotated open reading frames (ORFs). Three hundred thirty-four sporulation-essential genes were identified, including 78 novel ORFs and 115 known genes without previously described sporulation defects in the comprehensive Saccharomyces Genome (SGD) or Yeast Proteome (YPD) phenotype databases. We have further divided the uncharacterized sporulation-essential genes into early, middle, and late stages of meiosis according to their requirement for IME1 induction and nuclear division. We believe this represents a nearly complete identification of the genes uniquely required for this complex cellular pathway. The set of genes identified in this phenotypic screen shows only limited overlap with those identified by expression-based studies.

Genes, Fungal↗
PubMed2001

Genomic analysis of the erythromycin resistance element Tn5398 from Clostridium difficile.

Clostridium difficile is a nosocomial pathogen that causes a range of chronic intestinal diseases, usually as a result of antimicrobial therapy. Macrolide-lincosamide-streptogramin B (MLS) resistance in C. difficile is encoded by the Erm B resistance determinant, which is thought to be located on a conjugative transposon, Tn5398. The 9630 bp Tn5398 element has been cloned and completely sequenced and its insertion site determined. Analysis of the resultant data reveals that Tn5398 is not a classical conjugative transposon but appears to be a mobilizable non-conjugative element. It does not carry any transposase or site-specific recombinase genes, nor any genes likely to be involved in conjugation. Furthermore, using PCR analysis it has been shown that isolates of C. difficile obtained from different geographical locations exhibit heterogeneity in the genetic arrangement of both Tn5398 and their Erm B determinants. These results indicate that genetic exchange and recombination between these determinants occurs in the clinical and natural environment.

Anti-Bacterial Agents↗
PubMed2005

Genomic analysis of Oenococcus oeni PSU-1 and its relevance to winemaking.

Oenococcus oeni is an acidophilic member of the Leuconostoc branch of lactic acid bacteria indigenous to wine and similar environments. O. oeni is commonly responsible for the malolactic fermentation in wine and due to its positive contribution is frequently used as a starter culture to promote malolactic fermentation. In collaboration with the Lactic Acid Bacteria Genome Consortium the genome sequence of O. oeni PSU-1 has been determined. The complete genome is 1,780,517 nt with a GC content of 38%. 1701 ORFs could be predicted from the sequence of which 75% were functionally classified. Consistent with its classification as an obligately heterofermentative lactic acid bacterium the PSU-1 genome encodes all the enzymes for the phosphoketolase pathway. Moreover, genes related to flavor modification in wine, such as malolactic fermentation capacity and citrate utilization were readily identified. The completion of the O. oeni genome marks a significant new phase for wine-related research on lactic acid bacteria in which the physiology, genetic diversity and performance of O. oeni starter cultures can be more rigorously examined.

Fermentation↗
PubMed2006

Genomic analysis of host-pathogen interaction between Fusarium graminearum and wheat during early stages of disease development.

Fusarium graminearum strains responsible for causing the plant disease Fusarium head blight vary greatly in their ability to cause disease and produce mycotoxins on wheat. With the goal of understanding fungal gene expression related to pathogenicity, three cDNA libraries were created by suppression subtractive hybridization using wheat heads inoculated with a highly aggressive strain and either water or a less aggressive strain of this pathogen. Eighty-four fungal genes expressed during initial disease development were identified. The probable functions of 49 of these genes could be inferred by bioinformatic analysis. Thirty-five ESTs had no known homologues in current databases and were not identified by ab initio gene prediction methods. These ESTs from infected wheat heads probably represent F. graminearum genes that previously were not annotated. Four genes represented in one of these libraries were selected for targeted gene replacement, leading to the characterization of a two-component response regulator homologue involved in pathogenicity of the fungus. The mutants for this gene showed reduced sporulation and delayed spread of Fusarium head blight on wheat.

Computational Biology↗
PubMed2005

Genomic analysis of metabolic pathway gene expression in mice.

BACKGROUND: A segregating population of (C57BL/6J x DBA/2J)F2 intercross mice was studied for obesity-related traits and for global gene expression in liver. Quantitative trait locus analyses were applied to the subcutaneous fat-mass trait and all gene-expression data. These data were then used to identify gene sets that are differentially perturbed in lean and obese mice. RESULTS: We integrated global gene-expression data with phenotypic and genetic segregation analyses to evaluate metabolic pathways associated with obesity. Using two approaches we identified 13 metabolic pathways whose genes are coordinately regulated in association with obesity. Four genomic regions on chromosomes 3, 6, 16, and 19 were found to control the coordinated expression of these pathways. Using criteria that included trait correlation, differential gene expression, and linkage to genomic regions, we identified novel genes potentially associated with the identified pathways. CONCLUSION: This study demonstrates that genetic and gene-expression data can be integrated to identify pathways associated with clinical traits and their underlying genetic determinants.

Adipose Tissue↗