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Results for “gene function”

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At least 325 records · Page 18Linked to original sources
PubMed2006

Snail1 gene function during early embryo patterning in mice.

Originally identified as one of two zygotically expressed genes required for gastrulation in Drosophila, the Snail gene and other family members play critical roles in vertebrate development. Functionally, these genes are thought to drive epithelial-mesenchymal transitions at several points during development, and also during the metastatic progression of cancer. Although the Snai2-null mouse is viable and fertile, the early embryonic lethality of Snai1-null mice has precluded the detailed analysis of Snai1 function after gastrulation. We have recently generated a conditional allele of the Snai1 gene and examined its function during the formation of the neural crest and establishment of the left-right axis. We uncovered new details regarding Snai1 function during gastrulation and left-right asymmetry determination, while surprisingly showing that neither the Snai1 nor Snai2 genes are essential for neural crest cell delamination. These results shed new light on the role of Snail family genes in early mouse development, and raise interesting questions concerning the diversity of gene function among vertebrate species.

Alleles↗
PubMed1980

DNA methylation and gene function.

In most higher organisms, DNA is modified after synthesis by the enzymatic conversion of many cytosine residues to 5-methylcytosine. For several years, control of gene activity by DNA methylation has been recognized as a logically attractive possibility, but experimental support has proved elusive. However, there is now reason to believe, from recent studies, that DNA methylation is a key element in the hierarchy of control mechanisms that govern vertebrate gene function and differentiation.

Animals↗
PubMed2003

Use of RNA interference to investigate gene function in the human filarial nematode parasite Brugia malayi.

We describe the successful use of the reverse genetic technique RNA interference (RNAi) to investigate gene function in the human filarial nematode parasite Brugia malayi. We used fluorescently labelled double stranded RNA (dsRNA) to demonstrate that 300 bp molecules are able to enter adult females in culture while they remain excluded from microfilariae (mf). We have developed an optimised microvolume culture system to allow the exposure of parasites to high concentrations of dsRNA for extended periods. Culturing of adult female parasites in this system for 24h does not significantly reduce parasite lifespan or mf release in culture. Three B. malayi genes, beta-tubulin (Bm-tub-1), RNA polymerase II large subunit (Bm-ama-1) and B. malayi mf sheath protein 1/mf22 (Bm-shp-1) were targeted by soaking adult female B. malayi in dsRNA complementary to these transcripts in the optimised culture system. Targeting of the two housekeeping genes Bm-tub-1 and Bm-ama-1 led to a reduction in the levels of their transcripts, as assessed by reverse transcriptase coupled PCR (RT-PCR), and resulted in parasite death in culture. In contrast, targeting of the Bm-shp-1 gene was not lethal to adult females in culture. A marked reduction in mf release was observed for shp-1 RNAi parasites compared to controls and in addition 50% of mf released did not have fully elongated sheaths. This "short" phenotype correlated with the loss of the stockpiled shp-1 transcript from developing mf in treated adult female gonads. From these data we conclude that RNAi may be a useful method for assessment of drug target potential of genes identified in filarial gene discovery projects.

Alternative Splicing↗
PubMed1999

Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis.

We describe a genetic mosaic system in Drosophila, in which a dominant repressor of a cell marker is placed in trans to a mutant gene of interest. Mitotic recombination events between homologous chromosomes generate homozygous mutant cells, which are exclusively labeled due to loss of the repressor. Using this system, we are able to visualize axonal projections and dendritic elaboration in large neuroblast clones and single neuron clones with a membrane-targeted GFP marker. This new method allows for the study of gene functions in neuroblast proliferation, axon guidance, and dendritic elaboration in the complex central nervous system. As an example, we show that the short stop gene is required in mushroom body neurons for the extension and guidance of their axons.

Animals↗
PubMed1986

An estrogen-responsive element derived from the 5' flanking region of the Xenopus vitellogenin A2 gene functions in transfected human cells.

In the human breast cancer cell line MCF-7, we observe estrogen induction of the stable transfected Xenopus vitellogenin A2 gene. An estrogen-responsive element (ERE) could be defined by using a vitellogenin-chloramphenicol acetyltransferase hybrid gene in transient transfection experiments. The ERE is located in the 5' flanking region and is able to confer estrogen inducibility to the thymidine kinase gene promoter. By 5' and 3' deletions we have determined a 35 bp sequence sufficient for high stimulation by estradiol. Even 18 bp give a small estrogen response. The 35 bp ERE contains the palindromic sequence 5'GGTCACAGTGACC-3' as an essential element. The fact that the ERE of a frog gene functions in human cells demonstrates that signals and factors involved in the control have been conserved during evolution.

Acetyltransferases↗
PubMed2002

In silico approaches to microarray-based disease classification and gene function discovery.

The automated analysis of transcriptional profiling data promises a wealth of information that may be used to develop a more complete understanding of gene function and interactions. Moreover, it may improve the effectiveness of complex diagnostic tasks. This article discusses important data mining and management techniques to analyse genome-wide expression data. It reviews some of the major discovery goals, methods and applications in a number of biomedical domains. Finally, this paper highlights key problems that need to be approached by a new generation of computational solutions.

Algorithms↗
PubMed2002

Analysis of gene function in the zebrafish retina.

Mutagenesis screens in zebrafish have uncovered several hundred mutant alleles affecting the development of the retina and established the zebrafish as one of the leading models of vertebrate eye development. In addition to forward genetic mutagenesis approaches, gene function in the zebrafish embryo is being studied using several reverse genetic techniques. Some of these rely on the overexpression of a gene product, others take advantage of antisense oligonucleotides to block function of selected loci. Here we describe these methods in the context of the developing eye.

Animals↗
PubMed2003

Adenovirus-mediated functional gene transfer into parathyroid cells in vivo and in vitro.

Chronic renal failure patients usually develop secondary hyperparathyroidism and, as the disease progresses, there is a decrease in the number of vitamin D and calcium-sensing receptors (CaRs) in the parathyroid glands. Parathyroid cell function can be controlled if a functional gene is transferred into these cells using an adenovirus vector. Vitamin D or CaR genes transferred by the infected adenovirus vector induced a reduction in parathyroid hormone secretion. These results suggest that adenovirus-mediated gene transfer is a useful technique for control of parathyroid cell function.

Adenoviridae↗
PubMed2000

Chemical genetics: ligand-based discovery of gene function.

Chemical genetics is the study of gene-product function in a cellular or organismal context using exogenous ligands. In this approach, small molecules that bind directly to proteins are used to alter protein function, enabling a kinetic analysis of the in vivo consequences of these changes. Recent advances have strongly enhanced the power of exogenous ligands such that they can resemble genetic mutations in terms of their general applicability and target specificity. The growing sophistication of this approach raises the possibility of its application to any biological process.

Animals↗
PubMed2003

Screening for functional genes related to a novel gene, AngRem104, in human mesangial cells by cDNA microarray.

AngRem104 is a novel gene recently identified in human mesangial cells induced by angiotensin II. cDNA microarray was performed to screen the functional genes related to AngRem104. Thirty-one genes were up-regulated while 2 genes were down-regulated. Of all the up-regulated genes, fibronectin, one of the major extracellular matrixes, was up-regulated with over-expression of AngRem104.

Fibronectins↗
PubMed2006

TAR cloning: insights into gene function, long-range haplotypes and genome structure and evolution.

The structural and functional analysis of mammalian genomes would benefit from the ability to isolate from multiple DNA samples any targeted chromosomal segment that is the size of an average human gene. A cloning technique that is based on transformation-associated recombination (TAR) in the yeast Saccharomyces cerevisiae satisfies this need. It is a unique tool to selectively recover chromosome segments that are up to 250 kb in length from complex genomes. In addition, TAR cloning can be used to characterize gene function and genome variation, including polymorphic structural rearrangements, mutations and the evolution of gene families, and for long-range haplotyping.

Animals↗
PubMed2005

A global view of pleiotropy and phenotypically derived gene function in yeast.

Pleiotropy, the ability of a single mutant gene to cause multiple mutant phenotypes, is a relatively common but poorly understood phenomenon in biology. Perhaps the greatest challenge in the analysis of pleiotropic genes is determining whether phenotypes associated with a mutation result from the loss of a single function or of multiple functions encoded by the same gene. Here we estimate the degree of pleiotropy in yeast by measuring the phenotypes of 4710 mutants under 21 environmental conditions, finding that it is significantly higher than predicted by chance. We use a biclustering algorithm to group pleiotropic genes by common phenotype profiles. Comparisons of these clusters to biological process classifications, synthetic lethal interactions, and protein complex data support the hypothesis that this method can be used to genetically define cellular functions. Applying these functional classifications to pleiotropic genes, we are able to dissect phenotypes into groups associated with specific gene functions.

Algorithms↗
PubMed1983

Physical location of a herpes simplex virus type-1 gene function(s) specifically associated with a 10 million-fold increase in HSV neurovirulence.

In this paper we present a technique developed to physically locate the HSV-1 gene(s) which restore neurovirulence to a non-neurovirulent HSV intertypic recombinant described in the preceding report. In brief, tissue culture cells are co-transfected with unit length RE6 DNA and restriction endonuclease fragmented HSV-1 (strain 17 Syn+) DNA. In this way, random recombinations between RE6 and 17 Syn+ are produced. An in vivo enrichment in mouse brains is then employed to select recombinants which have incorporated the HSV-1 gene(s) associated with neurovirulence. In each of five cases where neurovirulent recombinants were isolated by this procedure, restriction enzyme and Southern DNA transfer analysis revealed that HSV-1 information from 0.71 to 0.83 map units had been incorporated into the RE6 genome. Confirmation of the role of this portion of the genome for HSV neurovirulence was obtained by similar cotransfection and in vivo rescue experiments performed with an electrophoretically purified HSV-1 DNA fragment which encompasses this region. Subsequent genome structure analysis of neurovirulent recombinants generated by this procedure revealed that only type-1 information from 0.71 to 0.83 map units had been incorporated into RE6. Thus an HSV-1 gene function(s) which resides in this region of the viral DNA is associated with a 10 million-fold increase in the neurovirulence of the virus. Potential applications of this in vivo selection technique are discussed.

Animals↗
PubMed1999

The maize tha4 gene functions in sec-independent protein transport in chloroplasts and is related to hcf106, tatA, and tatB.

Proteins are translocated across the chloroplast thylakoid membrane by a variety of mechanisms. Some proteins engage a translocation machinery that is derived from the bacterial Sec export system and require an interaction with a chloroplast-localized SecA homologue. Other proteins engage a machinery that is SecA-independent, but requires a transmembrane pH gradient. Recently, a counterpart to this Delta pH mechanism was discovered in bacteria. Genetic studies revealed that one maize protein involved in this mechanism, HCF106, is related in both structure and function to the bacterial tatA and tatB gene products. We describe here the mutant phenotype and molecular cloning of a second maize gene that functions in the Delta pH mechanism. This gene, thylakoid assembly 4 (tha4), is required specifically for the translocation of proteins that engage the Delta pH pathway. The sequence of the tha4 gene product resembles those of the maize hcf106 gene and the bacterial tatA and tatB genes. Sequence comparisons suggest that tha4 more closely resembles tatA, and hcf106 more closely resembles tatB. These findings support the notion that this sec-independent translocation mechanism has been highly conserved during the evolution of eucaryotic organelles from bacterial endosymbionts.

Amino Acid Sequence↗
PubMed2003

An efficient gene transduction system for studying gene function in primary human dermal fibroblasts and epidermal keratinocytes.

One of the critical challenges for cellular genetic studies in primary human skin cells is lack of a gene delivery system that provides efficient transduction and sustained expression of the transgenes. Due to the limited time of survival in culture, the processes of drug selection and clonal expansion for establishing gene stably expressing cell lines are not a realistic option for primary skin cells. We have examined various gene transduction techniques in primary dermal fibroblasts and epidermal keratinocytes of human skin. We report here that vectors based on the human immunodeficiency virus (HIV, lentivirus) offer more than 90% gene transduction efficiency and sustained expression of transgenes in both human skin cell types. In contrast, most of the commonly used techniques have at best 30% transduction efficiency in these cells. Using two previously reported migration control genes, protein kinase Cdelta and p38alpha-MAPK, as examples, we provide evidence that the unprecedented efficiency of the lentiviral system enables a clear detection of the genes' dominant negative effects, which are otherwise greatly compromised by ordinary transfection techniques. We believe that a wide application of this gene transduction system will greatly benefit studies of gene function in human skin cells.

Fibroblasts↗
PubMed1991

Segmental exchange between MHC class I genes in a higher primate: recombination in the gorilla between the ancestor of a human non-functional gene and an A locus gene.

Classical human major histocompatibility complex (MHC) class I molecules are the products of highly diverse gene loci. It has been suggested that segmental exchange may play a role in the generation of diversity at the antigen recognition site of MHC class I molecules. Here we present the cloning, sequencing and expression of two gorilla A locus cDNAs. One of these cDNAs shows remarkable similarity to the non-functional HLA-AR locus gene (5.4-LBF) only in exon 2. The remainder of the cDNA, however, is most closely related to other classical higher primate A locus genes. This suggests that a segmental exchange may have occurred between the ancestor of the non-functional HLA-AR gene and a classical gorilla A locus gene. Furthermore, the recombination event resulting in Gogo-A3 has affected its antigen recognition site. These data, therefore, demonstrate that segmental exchange can generate diversity at the antigen recognition sites of primate MHC class I molecules and suggest that non-functional genes can contribute to the generation of diversity of classical MHC class I genes.

Animals↗
PubMed2001

Mapping and identification of essential gene functions on the X chromosome of Drosophila.

The Drosophila melanogaster genome consists of four chromosomes that contain 165 Mb of DNA, 120 Mb of which are euchromatic. The two Drosophila Genome Projects, in collaboration with Celera Genomics Systems, have sequenced the genome, complementing the previously established physical and genetic maps. In addition, the Berkeley Drosophila Genome Project has undertaken large-scale functional analysis based on mutagenesis by transposable P element insertions into autosomes. Here, we present a large-scale P element insertion screen for vital gene functions and a BAC tiling map for the X chromosome. A collection of 501 X-chromosomal P element insertion lines was used to map essential genes cytogenetically and to establish short sequence tags (STSs) linking the insertion sites to the genome. The distribution of the P element integration sites, the identified genes and transcription units as well as the expression patterns of the P-element-tagged enhancers is described and discussed.

Animals↗
PubMed1989

Molecular cloning and expression of the functional gene encoding the M2 subunit of mouse ribonucleotide reductase: a new dominant marker gene.

Mammalian ribonucleotide reductase consists of two non-identical subunits, proteins M1 and M2. M2-related DNA sequences are present on mouse chromosomes 4, 7, 12 and 13. However, M2-overproducing mouse cells show amplification of a chromosome 12-specific, single 13 kb HindIII fragment, which probably represents the active gene. We have isolated this fragment from parental mouse cell DNA and used it to clone and characterize the functional M2 gene. The 5770 bp transcribed M2 sequence contains ten exons separated by nine 95-917 bp introns. The 501 bp of 5' flanking DNA is G + C rich and contains TTTAAA and CCAAT sequences as well as potential Sp1 binding sites. The M2-related sequence on chromosome 13, which contains only the last six exons and several internal rearrangements, is a pseudogene. Transfection of BALB/3T3 cells with the M2 gene resulted in stable transformants with a 10-fold reduction in sensitivity to hydroxyurea, compared to control cells. This confirmed that the cloned M2 genomic DNA represents the functional gene and conclusively establishes the link between hydroxyurea resistance and M2 expression in mammalian cells. M2 genomic DNA should be a valuable dominant, selectable marker for identifying and isolating stable co-transformants.

Animals↗