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 1,171 records · Page 65Linked to original sources
PubMed1998

[Structure and function of saw1--a gene related to differentiation of Streptomyces ansochromogenes].

The DNA sequence of double strands of saw1 gene was determined by the method of chaintermination inhibitors. The result indicated that the 1500 bp of DNA fragment displayed a complete open reading frame (ORF), the encoding regions were located in 419 to 1252 bp positions, saw1 product has 89% identity to amino acids of sigma whiG of Streptomyces coelicolor. When recombinant plasmid containing a 1500 bp saw1 DNA fragment insert in plasmid pIJ702 was introduced into Streptomyces coelicolor C71, the sporulation deficient mutant C71 could form spore and produce grey pigment. The gene function was studied by using the method of gene disruption and the result showed that the saw1 played an important role in developmental changes from aerial hypha to spore formation of Streptomyces ansochromogenes.

Amino Acid Sequence↗
PubMed2006

Structure of the catfish IGH locus: analysis of the region including the single functional IGHM gene.

The catfish IGH locus is large ( approximately 1 Mb) and complex, having undergone multiple internal duplications and transpositions. To define the structure of the locus that contains the single expressed IGHM gene, two overlapping bacterial-artificial-chromosome (BAC) clones spanning the most 3' end of the channel catfish immunoglobulin heavy (IGH) chain locus have been completely sequenced. The analyses created a contig of 257,153 bp containing 55 VH, 6 D, 12 JH genes and the IGH constant region genes encoding the functional secreted and membrane forms of IgM and the membrane form of IgD. This analysis revealed three major features. First, no C-region genes were found aside from the previously described IGHM1 and IGHD1, with the latter gene being the most 3' C-region gene of the catfish IGH locus. There was no evidence in the region sequenced for genes that could encode an Ig class similar to the IgZ/IgT described in zebrafish, trout and pufferfish. Second, there are a high number of VH pseudogenes, 28 out of 55 (51%). In contrast, the entire zebrafish IGH locus has 40 functional VH genes and eight pseudogenes (17%). Third, an internal duplication of a 52.4-kb block of VH genes has occurred. These observations suggest that the IGH locus of teleost fish varies significantly from species to species in the diversity of C-region genes as well as the numbers of genes encoding V regions.

Amino Acid Sequence↗
PubMed2000

Inhibition of debrisoquine hydroxylation with quinidine in subjects with three or more functional CYP2D6 genes.

AIMS: To study whether the CYP2D6 capacity in ultrarapid metabolizers of debrisoquine due to duplication/multiduplication of a functional CYP2D6 gene, can be 'normalised' by low doses of the CYP2D6 inhibitor quinidine and whether this is dose-dependent. METHODS: Five ultrarapid metabolizers of debrisoquine with 3, 4 or 13 functional CYP2D6 genes were given single oral doses of 5, 10, 20, 40, 80 and 160 mg quinidine. Four hours after quinidine intake, 10 mg debrisoquine was given. Urine was collected for 6 h after debrisoquine administration. Debrisoquine and its 4-hydroxymetabolite were analysed by h.p.l.c. and the debrisoquine metabolic ratio (MR) was calculated. RESULTS: Without quinidine the MR in the ultrarapid metabolizers ranged between 0.01 and 0.07. A dose-effect relationship could be established for quinidine with regard to the inhibitory effect on CYP2D6 activity. To reach an MR of 1-2, subjects with 3 or 4 functional genes required a quinidine dose of about 40 mg, while the sister and brother with 13 functional genes required about 80 mg quinidine. After 160 mg quinidine, the MRs, in the subjects with 3, 3, 4, 13 and 13 functional genes, were 12.6, 10.1, 9.2, 2.4 and 2.2, respectively. CONCLUSIONS: A dose-effect relationship could be established for quinidine inhibition of CYP2D6 in ultrarapid metabolizers. The clinical use of low doses of quinidine as an inhibitor of CYP2D6 might be considered in ultrarapid metabolizers taking CYP2D6 metabolized drugs rather than giving increased doses of the drug. Normalizing the metabolic capacity of CYP2D6, by giving a low dose of quinidine, may solve the problem of 'treatment resistance' caused by ultrarapid metabolism.

Administration, Oral↗
PubMed1979

Requirement of adenovirus type 12 gene 401 function for initiation of virus DNA synthesis.

The highly oncogenic human adenovirus type 12 temperature sensitive mutant. H12ts401, is unable to maintain the growth characteristics of transformed cells at the non-permissive temperature. In lytic infection, the 401 gene function is required to produce virus DNA. In the present study, virus DNA synthesized in ts401-infected human cells after temperature shift-up was characterized. No apparent suppression of DNA chain elongation or ligation occurs at the non-permissive temperature, but, as shown by density labelling, new initiation of virus DNA replication is inhibited under this condition. The results indicate that the 401 gene function is involved in the initiation of virus DNA synthesis in the lytic cycle.

Adenoviruses, Human↗
PubMed2004

Consensus clustering and functional interpretation of gene-expression data.

Microarray analysis using clustering algorithms can suffer from lack of inter-method consistency in assigning related gene-expression profiles to clusters. Obtaining a consensus set of clusters from a number of clustering methods should improve confidence in gene-expression analysis. Here we introduce consensus clustering, which provides such an advantage. When coupled with a statistically based gene functional analysis, our method allowed the identification of novel genes regulated by NFkappaB and the unfolded protein response in certain B-cell lymphomas.

Cluster Analysis↗
PubMed1995

Genetic footprinting: a genomic strategy for determining a gene's function given its sequence.

This report describes an efficient strategy for determining the functions of sequenced genes in microorganisms. A large population of cells is subjected to insertional mutagenesis. The mutagenized population is then divided into representative samples, each of which is subjected to a different selection. DNA is prepared from each sample population after the selection. The polymerase chain reaction is then used to determine retrospectively whether insertions into a particular sequence affected the outcome of any selection. The method is efficient because the insertional mutagenesis and each selection need only to be performed once to enable the functions of thousands of genes to be investigated, rather than once for each gene. We tested this "genetic footprinting" strategy using the model organism Saccharomyces cerevisiae.

Amino Acids↗
PubMed1988

A bacteriophage T4 gene which functions to inhibit Escherichia coli Lon protease.

A bacteriophage T4 gene which functions to inhibit Escherichia coli Lon protease has been identified. This pin (proteolysis inhibition) gene was selected for its ability to support plaque formation by a lambda Ots vector at 40 degrees C. Southern blot experiments indicated that this T4 gene is included within the 4.9-kilobase XbaI fragment which contains gene 49. Subcloning experiments showed that T4 gene 49.1 (designated pinA) is responsible for the ability of the Ots vector to form plaques at 40 degrees C. Deficiencies in Lon protease activity are the only changes known in E. coli that permit lambda Ots phage to form plaques efficiently at 40 degrees C. lon+ lysogens of the lambda Ots vector containing pinA permitted a lambda Ots phage to form plaques efficiently at 40 degrees C. Furthermore, these lysogens, upon comparison with similar lysogens lacking any T4 DNA, showed reduced levels of degradation of puromycyl polypeptides and of canavanyl proteins. The lon+ lysogens that contained pinA exhibited other phenotypic characteristics common to lon strains, such as filamentation and production of mucoid colonies. Levels of degradation of canavanyl proteins were essentially the same, however, in null lon lysogens which either contained or lacked pinA. We infer from these data that the T4 pinA gene functions to block Lon protease activity; pinA does not, however, appear to block the activity of proteases other than Lon that are involved in the degradation of abnormal proteins.

ATP-Dependent Proteases↗
PubMed1985

Mutant alleles at the locus elav in Drosophila melanogaster lead to nervous system defects. A developmental-genetic analysis.

We report a developmental and genetic analysis of the X-linked vital locus l(1)EC7 in Drosophila melanogaster. The locus maps in the salivary band region 1B4-5 to 1B8-9, a part of the X chromosome previously shown to be essential for normal neural development. Certain mutant alleles at the locus can cause embryonic lethality, indicating that the function provided by the gene is essential during embryogenesis. A developmental analysis of gynandromorphic genetic mosaics shows that: (1) the gene function is autonomously essential in the eye; (2) the gene function is essential for normal development of the optic lobes; and (3) the gene function is not necessary in most major imaginal-disc cell derivatives with the exception of the eye disc. Conclusions from the developmental analysis of a temperature sensitive allele are consistent with those from the mosaic analysis. The embryonic lethality caused by the mutant alleles and abnormalities observed in the genetic mosaics have led us to rename the locus l(1)EC7 to elav (embryonic lethal, abnormal visual system).

Alleles↗
PubMed1998

Hox genes, homeosis and the evolution of segment identity: no need for hopeless monsters.

Significant changes have occurred in the developmental role of Hox genes, even within groups of arthropods that already have complex body plans and many different segment types. This is hard to reconcile with the 'selector gene' model for Hox gene function. Selector genes act as stable binary switches that direct lineages of cells to adopt alternative developmental fates. This model suggests that the regulation of selector genes can only evolve through mutations that alter the identity of whole developmental compartments -in the case of Hox genes, whole segments. Once segments have evolved distinct morphology and function, such mutations will result in dramatic homeotic transformations that are unlikely to be tolerated by natural selection. Thus we would expect the developmental role of these "master control genes" to become frozen as body plans become more complex. I argue for a revised model for the role and regulation of the Hox genes. This provides alternative mechanisms for evolutionary change, that may lead to incremental changes in segment morphology. The summation of such changes over long periods of time would result in differences in Hox gene function between taxa comparable to the effects of gross homeotic mutations, without the need to invoke the selective advantage of hopeful monsters.

Abnormalities, Multiple↗
PubMedDate not supplied

The ghost of selection past: rates of evolution and functional divergence of anciently duplicated genes.

The duplication of genes and even complete genomes may be a prerequisite for major evolutionary transitions and the origin of evolutionary novelties. However, the evolutionary mechanisms of gene evolution and the origin of novel gene functions after gene duplication have been a subject of many debates. Recently, we compiled 26 groups of orthologous genes, which included one gene from human, mouse, and chicken, one or two genes from the tetraploid Xenopus and two genes from zebrafish. Comparative analysis and mapping data showed that these pairs of zebrafish genes were probably produced during a fish-specific genome duplication that occurred between 300 and 450 Mya, before the teleost radiation (Taylor et al. 2001). As discussed here, many of these retained duplicated genes code for DNA binding proteins. Different models have been developed to explain the retention of duplicated genes and in particular the subfunctionalization model of Force et al. (1999) could explain why so many developmental control genes have been retained. Other models are harder to reconcile with this particular set of duplicated genes. Most genes seem to have been subjected to strong purifying selection, keeping properties such as charge and polarity the same in both duplicates, although some evidence was found for positive Darwinian selection, in particular for Hox genes. However, since only the cumulative pattern of nucleotide substitutions can be studied, clear indications of positive Darwinian selection or neutrality may be hard to find for such anciently duplicated genes. Nevertheless, an increase in evolutionary rate in about half of the duplicated genes seems to suggest that either positive Darwinian selection has occurred or that functional constraints have been relaxed at one point in time during functional divergence.

Amino Acid Sequence↗
PubMed2003

Genes for chlorogenate and hydroxycinnamate catabolism (hca) are linked to functionally related genes in the dca-pca-qui-pob-hca chromosomal cluster of Acinetobacter sp. strain ADP1.

Hydroxycinnamates are ubiquitous in the environment because of their contributions to the structure and defense mechanisms of plants. Additional plant products, many of which are formed in response to stress, support the growth of Acinetobacter sp. strain ADP1 through pathways encoded by genes in the dca-pca-qui-pob chromosomal cluster. In an appropriate genetic background, it was possible to select for an Acinetobacter strain that had lost the ability to grow with caffeate, a commonly occurring hydroxycinnamate. The newly identified mutation was shown to be a deletion in a gene designated hcaC and encoding a ligase required for conversion of commonly occurring hydroxycinnamates (caffeate, ferulate, coumarate, and 3,4-dihydroxyphenylpropionate) to thioesters. Linkage analysis showed that hcaC is linked to pobA. Downstream from hcaC and transcribed in the direction opposite the direction of pobA transcription are open reading frames designated hcaDEFG. Functions of these genes were inferred from sequence comparisons and from the properties of knockout mutants. HcaD corresponded to an acyl coenzyme A (acyl-CoA) dehydrogenase required for conversion of 3,4-dihydroxyphenylpropionyl-CoA to caffeoyl-CoA. HcaE appears to encode a member of a family of outer membrane proteins known as porins. Knockout mutations in hcaF confer no discernible phenotype. Knockout mutations in hcaG indicate that this gene encodes a membrane-associated esterase that hydrolyzes chlorogenate to quinate, which is metabolized in the periplasm, and caffeate, which is metabolized by intracellular enzymes. The chromosomal location of hcaG, between hcaC (required for growth with caffeate) and quiA (required for growth with quinate), provided the essential clue that led to the genetic test of HcaG as the esterase that produces caffeate and quinate from chlorogenate. Thus, in this study, organization within what is now established as the dca-pca-qui-pob-hca chromosomal cluster provided essential information about the function of genes in the environment.

Acinetobacter↗
PubMed2001

Interruption of coding sequences by heterologous introns can enhance the functional expression of recombinant genes.

Sustained expression of recombinant proteins is a critical factor for the effectiveness of numerous applications in the biomedical sciences including the treatment of human disease by gene therapy, the large scale production of therapeutic proteins, as well as the investigation of gene function by transgenesis or cell type specific mutagenesis. Although much attention has been paid to the optimisation of regulatory sequences such as promoters, untranslated regions and polyadenylation signals, effective and sustained expression of recombinant genes in vivo is often difficult to achieve. Here we report that the creation of artificial exons, by insertion of two short heterologous introns into open reading frames, is not only compatible with functional expression, but also leads to a 30-fold enhancement of mRNA production for both green fluorescent protein and the bacteriophage P1-derived Cre recombinase. The levels of green fluorescence were increased five-fold in cell lines and sustained long-term expression at increased levels was observed in rat brain after transduction with a herpes simplex virus-based vector. The data presented identify a means by which the expression of recombinant genes can be enhanced considerably, in addition to and independently from the surrounding regulatory sequences. The method should help obtain sustained and effective expression of recombinant proteins in vivo.

Animals↗
PubMed1999

Double-stranded RNA induces specific developmental defects in zebrafish embryos.

Treatment with double-stranded RNA (dsRNA) has been shown to interfere with the function of specific genes in various invertebrate species. However, it has not yet been reported that this technique can be applied to vertebrates as well. We have investigated whether dsRNA treatment will inhibit gene function in zebrafish embryos. By microinjecting dsRNA corresponding to three genetically characterised genes we produced embryonic defects that were similar to the known mutant phenotypes of these loci. The efficiency of inducing specific defects (20-30%) was about 10-fold higher than in experiments with antisense RNA. We also observed that the level of the endogenous mRNA in zebrafish embryos was substantially reduced throughout the embryo following dsRNA injection. However, the interference of gene function showed a strong dependence on the amount of dsRNA. These findings suggest that dsRNA-mediated interference will become an important tool for analysing the functional roles of genes in zebrafish and other vertebrates.

Animals↗
PubMed1992

Purification and characterization of seven chloroplast ribosomal proteins: evidence that organelle ribosomal protein genes are functional and that NH2-terminal processing occurs via multiple pathways in chloroplasts.

Putative genes for 21 ribosomal proteins (RPs) have been identified in the chloroplast DNA of four plants by nucleotide sequencing and homology comparison but few of the gene products have been characterized. Here we report the purification and N-terminal sequencing of seven proteins from the spinach chloroplast ribosome. The data show them to be the homologues of Escherichia coli RPs L20, L32, L33, L36, S12, S16 and S19, and thus support the view that their genes identified in the chloroplast DNA represent functional genes. The initiating methionine residue was not detected in the mature protein in most cases but it was present in S16, indicating that only the formyl group is removed in this case. This result and the previously reported finding of N-methyl alanine at the N-terminus of chloroplast L2 indicate the existence of multiple N-terminal processing pathways in the chloroplast.

Amino Acid Sequence↗
PubMed1996

SpHbox7, a new Abd-B class homeobox gene from the sea urchin Strongylocentrotus purpuratus: insights into the evolution of hox gene expression and function.

Hox genes, by virtue of their key functions in axial patterning, have long been thought to be pivotal players in the evolution of developmental mechanisms. Despite their potential importance in evolution, there is little information about Hox genes in animal groups that are most closely related to ancestral Chordates. Accordingly, we have taken the step of analyzing Hox gene expression and function in the sea urchin embryo, whose simple bilateral body plan is thought to resemble that of a stem organism in the Chordate lineage. Here we describe the isolation, sequences analysis and spatiotemporal expression pattern of a sea urchin (Strongylocentrotus purpuratus) Abd-B-like gene, designated SpHbox7. We show that this gene is one of at least two Abd-B-like genes in the S. purpuratus genome, a result that argues against the simple hypothesis that Hox gene duplications occurred only during the evolution of the chordates. SpHbox7 transcripts are first detectable in midblastula stage embryos, increase in amount during gastrulation, decline slightly by the pluteus stage, and are not detectable in any tissue of the adult. Whole mount in situ hybridization and antibody staining with an SpHbox7-specific antibody reveal that both SpHbox7 mRNA and protein are present throughout the embryo in the blastula. Subsequently, they are localized in the invaginating archenteron, secondary mesenchyme, and oral ectoderm. By the pluteus larva stage, SpHbox7 protein and mRNA are present in the gut, larval arms, and portions of the oral ectoderm. This complex and dynamic expression pattern suggests that SpHbox7 has a role in the patterning of the gut, the mesoderm, and the oral surface.

Aging↗
PubMed1990

Identification of the functional profilin gene, its localization to chromosome subband 17p13.3, and demonstration of its deletion in some patients with Miller-Dieker syndrome.

Profilin is a conserved actin-monomer-binding protein which is found in all eukaryotes, including yeast. Although amino acid sequence analysis and RNase protection analysis suggest a single profilin isoform in mammalian cells, Southern blot analysis of human and somatic cell hybrid DNA indicates several loci in the human genome which hybridize with the profilin cDNA. We therefore isolated human genomic clones to analyze these genetic loci in detail. Only one of the cloned loci has typical features of a functional gene, including upstream transcriptional elements and typical exon-intron structure. Four other isolated loci are all diverged, intronless pseudogenes and are likely to be nonfunctional. The functional gene was localized to human chromosome band 17p13 by analysis of somatic cell hybrids and by in situ chromosomal localization. The Miller-Dieker syndrome (MDS), a rare congenital disorder manifested by characteristic facial abnormalities and lissencephaly (smooth brain), is associated with microdeletions of the distal 17p region. RFLP analysis of a patient with MDS, and analysis of somatic cell hybrids containing partially deleted chromosomes 17 from patients with MDS, using the profilin gene probe, indicate that profilin is localized to chromosome subband 17p13.3. These results also indicate that profilin is the first identified cloned gene which is part of the genetic material deleted in some patients with MDS but that other patients have smaller deletions not affecting the profilin locus. Thus, single allelic deletion of the profilin locus may contribute to the clinical phenotype of the MDS in some patients but does not play a major role in the essential phenotype.

Amino Acid Sequence↗
PubMed2001

Functional analysis of pathogenicity genes in a genomics world.

Genome-wide mutational and expression analyses have been performed in yeast and provide a model for large-scale analysis of gene function in filamentous fungi. The recent completion of the Neurospora crassa genome offers a resource for comparative analysis with plant pathogenic filamentous fungi. These advances have important implications for molecular genetic studies of pathogenicity genes.

Fungal Proteins↗
PubMed2006

Modeling chromosomes in mouse to explore the function of genes, genomic disorders, and chromosomal organization.

One of the challenges of genomic research after the completion of the human genome project is to assign a function to all the genes and to understand their interactions and organizations. Among the various techniques, the emergence of chromosome engineering tools with the aim to manipulate large genomic regions in the mouse model offers a powerful way to accelerate the discovery of gene functions and provides more mouse models to study normal and pathological developmental processes associated with aneuploidy. The combination of gene targeting in ES cells, recombinase technology, and other techniques makes it possible to generate new chromosomes carrying specific and defined deletions, duplications, inversions, and translocations that are accelerating functional analysis. This review presents the current status of chromosome engineering techniques and discusses the different applications as well as the implication of these new techniques in future research to better understand the function of chromosomal organization and structures.

Aneuploidy↗