Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “gene function”

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 1,747 records · Page 97Linked to original sources
PubMed1991

A functional and structural analysis of the Sex combs reduced locus of Drosophila melanogaster.

We have undertaken a developmental genetic analysis of the homeotic gene Sex combs reduced (Scr) of Drosophila melanogaster by examining embryonic and adult phenotypes of mutations affecting Scr gene function. Molecular mapping of Scr breakpoint lesions has defined a segment of greater than 70 kb of DNA necessary for proper Scr gene function. This region is split by the fushi tarazu (ftz) gene, with lesions affecting embryonic Scr function molecularly mapping to the region proximal (5') to ftz and those exhibiting polyphasic semilethality predominantly mapping distal (3') to ftz. Gain-of-function mutations are associated with genomic rearrangements and map throughout the Scr locus. Our analysis has revealed that the Scr locus encompasses genetic elements that are responsible for functions in both the embryonic and larval to adult periods of development. From these studies, we conclude that Scr is a complex genetic locus with an extensive regulatory region that directs functions required for normal head and thoracic development in both the embryo and the adult and that the regulation of Scr during these two periods is distinct.

Alleles↗
PubMed2001

Extreme hydrops fetalis and cardiovascular abnormalities in mice lacking a functional Adrenomedullin gene.

Adrenomedullin, a recently identified potent vasodilator, is expressed widely and has been suggested to have functions ranging from reproduction to blood pressure regulation. To elucidate these functions and define more precisely sites of Adm expression, we replaced the coding region of the Adm gene in mice with a sequence encoding enhanced green fluorescent protein while leaving the Adm promoter intact. We find that Adm(-/-) embryos die at midgestation with extreme hydrops fetalis and cardiovascular abnormalities, including overdeveloped ventricular trabeculae and underdeveloped arterial walls. These data suggest that genetically determined absence of Adm may be one cause of nonimmune hydrops fetalis in humans.

Abnormalities, Multiple↗
PubMed1994

Mutations of the neurofibromatosis type 2 gene and lack of the gene product in vestibular schwannomas.

Schwannomas are common tumors of the nervous system and are frequently found in patients with neurofibromatosis (NF) 2. Although loss of heterozygosity in NF2 tumors suggests that the NF2 gene functions as a tumor suppressor gene, the NF2 gene shows amino acid sequence homology to structural proteins in one of which dominantly acting mutations have been described. We performed a mutational analysis in 30 vestibular schwannomas and examined the effect of mutations on the NF2 protein. We detected 18 mutations in 30 vestibular schwannomas of which seven contained loss or mutation of both NF2 alleles. Most mutations were predicted to result in a truncated protein. Mutational hot spots were not identified. Immunocytochemical studies using antibodies to the NF2 protein showed complete absence of staining in tumor Schwann cells, whereas staining was observed in normal vestibular nerve. These data indicate that loss of NF2 protein function is a necessary step in schwannoma pathogenesis and that the NF2 gene functions as a recessive tumor suppressor gene.

Amino Acid Sequence↗
PubMed2007

Virus-induced gene silencing in plant roots.

Virus-induced gene silencing (VIGS) has been used as a quick and easy tool to assess gene function in plants. The virus, carrying a portion of an endogenous gene, triggers a homology-based defense mechanism when introduced into plants. Infection with the modified virus results in gene-specific transcript degradation. Several virus-based vectors have been developed for use in VIGS. One of these virus vectors, tobacco rattle virus (TRV), has a large host range and is transmitted by phytopathogenic nematodes of the genera Trichodorus and Paratrichodorus. TRV has been used in VIGS to study gene function in above-ground parts of plants. This chapter describes a protocol for the use of TRV vector to silence genes in roots.

Gene Expression Regulation, Plant↗
PubMed2003

Functional genomics and radioisotope-based imaging procedures.

After the sequencing of the human genome has been completed, non-invasive imaging studies are needed to assess the function of new genes in living organisms. The evaluation of genetically manipulated animals or new designed biomolecules will require a thorough understanding of physiology, biochemistry and pharmacology, and the experimental approaches will involve many new technologies including in vivo imaging with single photon emission computed tomography (SPECT) and positron emission tomography (PET). Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as enzymes, receptors, antigens or transporters. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging. Also, drug distribution studies for new therapeutic biomolecules are needed at least during preclinical stages of drug development. Clinical gene therapy needs non-invasive tools to evaluate the efficiency of gene transfer. These informations can be used for therapy planning, follow-up studies in treated tumors and as an indicator of prognosis. Therapy planning is performed by the assessment of gene expression for example using radio-labeled specific substrates to determine the activity of suicide enzymes such as the Herpes Simplex Virus thymidine kinase. Follow-up studies with single photon emission tomography or positron emission tomography may be done to evaluate early or late effects of gene therapy on tumor metabolism or proliferation. Finally, new biomolecules will be developed by bioengineering methods which may be used for isotope-based diagnosis and treatment of disease.

Gene Expression Regulation↗
PubMed2004

Angiopoietin-1 modulates endothelial cell function and gene expression via the transcription factor FKHR (FOXO1).

Despite genetic evidence establishing angiopoietin-1 (Ang-1) as an essential regulator of vascular development, the molecular mechanisms underlying Ang-1 function are almost completely uncharacterized. In this report, we demonstrate that Ang-1, via Akt activation, is a potent inhibitor of the forkhead transcription factor FKHR (FOXO1), identifying for the first time a nuclear signaling pathway through which Ang-1 modulates gene expression. We use microarray analysis to show that FKHR, whose function in endothelial cells has not previously been elucidated, regulates many genes associated with vascular destabilization and remodeling (including angiopoietin-2, an Ang-1 antagonist) and endothelial cell apoptosis (e.g., survivin, TRAIL). Ang-1 inhibits FKHR-mediated changes in gene expression and FKHR-induced apoptosis. Analysis of gene expression changes induced by an activated version of Akt confirms that FKHR is a major target through which Akt regulates transcription in endothelial cells. We use RNA interference to demonstrate that FKHR is required for the expression of genes (including Ang-2) that have important vascular functions. Our data suggest a novel, tissue-specific role for the Akt/FKHR pathway in the vasculature and suggest a mechanistic basis for the previously described actions of Ang-1 as a regulator of endothelial cell survival and blood vessel stability.

Angiopoietin-1↗
PubMed1992

Isolation and characterization of sfp: a gene that functions in the production of the lipopeptide biosurfactant, surfactin, in Bacillus subtilis.

The sfp gene is required for cells of Bacillus subtilis to become producers of the lipopeptide antibiotic surfactin. sfp was isolated and its nucleotide sequence was determined. sfp was expressed in Escherichia coli and its putative product was purified for use in antibody production and in amino acid sequence analysis. The gene was plasmid-amplified in B. subtilis, where it conferred a Srf+ phenotype on sfp0 (surfactin non-producing) cells. Overproduction of Sfp in B. subtilis did not cause production of an increased amount of surfactin and resulted in the repression of a lacZ transcriptional fusion of the srfA operon, which encodes enzymes that catalyze surfactin synthesis. We propose that sfp represents an essential component of peptide synthesis systems and also plays a role, either directly or indirectly, in the regulation of surfactin biosynthesis gene expression.

Amino Acid Sequence↗
PubMed1994

Organization of the mouse 5-HT3 receptor gene and functional expression of two splice variants.

The structure of the mouse 5-HT3 receptor gene, 5-HT3R-A, is most similar to nicotinic acetylcholine receptor (nAChR) genes, in particular to the gene encoding the neuronal nAChR subunit alpha 7. These genes share among other things the location of three adjacent introns, suggesting that 5-HT3R-A and nAChR genes arose from a common precursor gene. The alternative use of two adjacent splice acceptor sites in intron 8 creates, in addition to the original 5-HT3R-A cDNA (5-HT3R-AL), a shorter isoform (5-HT3R-AS) which lacks six codons in the segment that translates into the major intracellular domain. This splice consensus sequence is not found in human genomic DNA. In mouse, we demonstrate by RNAse protection assay that 5-HT3R-AS mRNA is approximately 5 times more abundant than 5-HT3R-AL mRNA in both neuroblastoma cell lines and neuronal tissues. We used the Semliki Forest virus expression system for electrophysiological characterization of 5-HT3R-AS and 5-HT3R-AL in mammalian cells. No differences in electrophysiological characteristics, such as voltage dependence, desensitization kinetics, or unitary conductance were found between homomeric 5-HT3R-AS and 5-HT3R-AL receptors. Their properties are very similar to those of 5-HT3 receptors in mouse neuroblastoma cell lines.

Alternative Splicing↗
PubMed2004

Expression patterns of four different regulatory genes that function during sea urchin development.

The spatial and temporal expression patterns of Strongylocentrotus purpuratus genes encoding four different transcription factors, viz. SpFoxb, SpHes, SpKrl, and SpNk1, have been examined, using a recently developed, highly sensitive whole mount in situ hybridization procedure, and quantitative real time PCR. Two of the genes studied, SpHes and SpNk1, are newly isolated. Their expression patterns suggest the existence of previously unknown ectodermal domains. Re-examination of the expression pattern of SpFoxb reveals domains of expression not previously reported for this gene, and we also provide a more detailed, temporal and spatial description of the expression pattern of SpKrl than heretofore available.

Amino Acid Sequence↗
PubMed1992

Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences.

Genomic structure of the ME491/CD63 antigen gene and promoter activity of the 5'-flanking regulatory sequences were studied. The antigen gene consists of eight exons that span 4 kilobase-pairs. Primer extension analysis with RNA from cultured human cells identified three major transcription initiation sites. The 5'-flanking region of exon 1 has features characteristic to promoters of many house-keeping genes and growth-regulating genes. The region is highly GC rich and contains potential binding sites for transcription factors such as Sp1 and ETF, but not a TATA box. The 5'-flanking sequence exerted strong promoter activity when linked to a reporter gene. Deletion mutant analysis of the 5'-flanking sequence has strongly suggested that a potential binding site for AP-1 plays an important role in positively regulating the gene expression.

Amino Acid Sequence↗
PubMed2001

The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes.

The major murine systemic lupus erythematosus (SLE) susceptibility locus Sle1 is syntenic to a chromosomal region linked with SLE susceptibility in multiple human studies. Congenic analyses have shown that Sle1 breaks tolerance to chromatin, a necessary step for full disease induction that can be suppressed by specific modifier loci. In the present study, our fine mapping analysis of the location of Sle1 has determined that three loci within this congenic interval, termed Sle1a, Sle1b, and Sle1c, can independently cause a loss of tolerance to chromatin. Each displays a distinctive profile of serological and cellular characteristics, with T and B cell functions being more affected by Sle1a and Sle1b, respectively. The epistatic interactions of Sle1 with other susceptibility loci to cause severe nephritis cannot be accounted, however, by these three loci alone, suggesting the existence of an additional locus, termed Sle1d. These findings indicate that the potent autoimmune phenotype caused by the Sle1 genomic interval reflects the combined impact of four, separate, susceptibility genes. This level of genetic complexity, combined with similar findings in other systems, supports the possibility that many complex trait loci reflect the impact of polymorphisms in linked clusters of genes with related functions.

Animals↗
PubMed2003

Diversity of ascomycete laccase gene sequences in a southeastern US salt marsh.

The diversity of ascomycete laccase sequences was surveyed in a southeastern US salt marsh using a degenerate primer set designed around copper binding sites conserved in fungal laccases. This gene was targeted for diversity analysis because of its potential function in lignin degradation in the salt marsh ecosystem and because few studies have assessed functional gene diversity in natural fungal communities. Laccase sequences were amplified from genomic DNA extracted from 24 isolates (representing 10 ascomycete species) cultured from decaying blades of Spartina alterniflora, and from DNA extracted directly from the decaying blades. Among the ascomycete isolates, 21 yielded a PCR product of expected size (900 bp) that was tentatively identified as laccase based on sequence similarities to previously published laccase sequences from related organisms. Overall, 13 distinct sequence types, containing 39 distinct sequences, were identified among the isolates, with several species yielding multiple distinct laccase types. PCR amplifications from early and late decay blades of S. alterniflora yielded seven laccase types. Of these, five were composed of sequences >96% similar at the amino acid level to sequences from three cultured ascomycetes previously found to be dominant members of the fungal communities on decaying S. alterniflora blades. Two of the laccase types from the natural-decay clone library were novel and did not match any of the sequences obtained from the cultured ascomycetes. The 39 distinct sequences and 15 distinct laccase sequence types retrieved from the S. alterniflora decay system demonstrate high sequence diversity of this functional gene in a natural fungal community.

Amino Acid Sequence↗
PubMed2002

Global genome repair of 8-oxoG in hamster cells requires a functional CSB gene product.

Cockayne syndrome (CS) is an autosomal recessive human disease characterized by UV-sensitivity as well as neurological and developmental abnormalities. Two complementation groups have been established, designated CS-A and CS-B. Traditionally, CSA and CSB have been ascribed a function in the transcription-coupled repair (TCR) pathway of nucleotide excision repair (NER) that efficiently removes bulky lesions from the transcribed strand of RNA polymerase II transcribed genes. To assess the role of the CSB protein in the repair of the highly mutagenic base lesion 7,8-dihydro-8-oxoguanine (8-oxoG), we have investigated the removal of this lesion using an in vitro incision approach with cell extracts as well as an in vivo approach with a modified protocol of the gene-specific repair assay, which allows the measurement of base lesion repair in intragenomic sequences. Our results demonstrate that the integrity of the CSB protein is pivotal for processes leading to incision at the site of 8-oxoG and that the global genome repair (GGR) of this lesion requires a functional CSB gene product in vivo.

Adenosine Triphosphatases↗
PubMed1983

Four unique genes required for beta tubulin expression in vertebrates.

We have isolated the four separate segments of chicken DNA which contain sequence homology to beta tubulin. With the exception of a fifth region of DNA which appears to contain only a 5' fragment of a beta gene, these four cloned sequences represent all of the beta tubulin encoding DNA in the chicken. Each gene is very similar in structure, containing three or four small intervening sequences clustered in the 5' portion of the coding region. Using RNAs prepared from a variety of cell lines and tissues, we have found five different mRNAs which carry beta tubulin sequences, two of which are encoded by the same gene. Three of these mRNAs are unexpectedly long (between 3500 and 4000 bases). However, these large mRNAs do give authentic beta tubulin translation products. Overall, we conclude that each of the four beta tubulin genes is a functional gene which is expressed in a specific program during differentiation. These data strongly suggest that four beta tubulins are necessary for proper microtubule function in vertebrates.

Animals↗
PubMed1993

Structure and function of genes in the MHC class II region.

Genes required for antigen processing map to the MHC class II region. For the endogenous (class I) antigen processing pathway, many hypotheses concerning the structure and function of the corresponding gene products have been verified during the past year. The identity of the gene(s) involved in the exogenous (class II) pathway remains to be determined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

The promise of genomics to identify novel therapeutic targets.

The cataloguing of the human genome has provided an unprecedented prospectus for target identification and drug discovery. A current analysis indicates that slightly more than 3000 unique protein encoding loci are potentially amenable to pharmacological intervention (the 'druggable genome', which can be queried at http://function.gnf.org/druggable). However, the assessment of genome sequence data has not resulted in the anticipated acceleration of novel therapeutic developments. The basis for this shortfall lies in the significant attrition rates endemic to preclinical/clinical development, as well as the often underestimated complexity of gene function in higher order biological systems. To address the latter issue, a number of strategies have emerged to facilitate genomics-driven target identification and validation, including cellular profiling of gene function, in silico modelling of gene networks, and systematic analyses of protein complexes. The expectation is that the integration of these and other systems-based technologies may enable the conversion of potential genomic targets into functionally validated molecules, and result in practicable gene-based drug discovery pipelines.

Animals↗
PubMed2006

Heterosis and polymorphisms of gene expression in an elite rice hybrid as revealed by a microarray analysis of 9198 unique ESTs.

Despite the significant contributions of utilizing heterosis to crop productivity worldwide, the biological mechanisms of heterosis remained largely uncharacterized. In this study, we analyzed gene expression profiles of an elite rice hybrid and the parents at three stages of young panicle development, using a cDNA microarray consisting of 9198 expressed sequence tags (ESTs), with the objective to reveal patterns of gene expression that may be associated with heterosis in yield. A total of 8422 sequences showed hybridization signals in all three genotypes in at least one stage and 5771 sequences produced detectable signals in all slides. Significant differences in expression level were detected for 438 sequences among the three genotypes in at least one of the three stages, as determined by ANOVA validated with 100 permutations at P < 0.05. Significant mid-parent heterosis was detected for 141 sequences, which demonstrated the following features: a much larger number of sequences showed negative heterosis than ones showing positive heterosis; genes functioning in DNA replication and repair tended to show positive heterosis; genes functioning in carbohydrate metabolism, lipid metabolism, energy metabolism, translation, protein degradation, and cellular information processing showed negative heterosis; both positive and negative heterosis were observed for genes in amino acid metabolism, transcription, signal transduction, plant defense and transportation. The results are indicative of the biochemical and physiological activities taking place in the hybrid relative to the parents. Identification of genes showing expression polymorphisms among different genotypes and heterotic expression in the hybrid may provide new avenues for exploring the biological mechanisms underlying heterosis.

Analysis of Variance↗
PubMed1992

Identification of a mammalian gene structurally and functionally related to the CDC25 gene of Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae CDC25 gene encodes a nucleotide-exchange-factor (NEF) that can convert the inactive GDP-bound state of RAS proteins to an active RAS-GTP complex. CDC25 can activate the yeast RAS proteins as well as the human H-ras protein. CDC25 is a member of a family of yeast genes that likely encode NEFs capable of regulating the RAS-related proteins found in yeast. By aligning the amino acid sequence of CDC25-related gene products we found a number of conserved motifs. Using degenerate oligonucleotides that encode these conserved sequences, we have used polymerase chain reactions to amplify fragments of mouse and human cDNAs related to the yeast CDC25 gene. We show that a chimeric molecule, part mouse and part yeast CDC25, can suppress the loss of CDC25 function in the yeast S. cerevisiae.

Amino Acid Sequence↗