Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GENES”

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 199 records · Page 11Linked to original sources
PubMed1987

Class II genes of the human major histocompatibility complex. The DO beta gene is a divergent member of the class II beta gene family.

A novel class II beta chain gene is described. This gene, tentatively called DO beta, displays considerably less polymorphism than beta genes of the DP, DQ, and DR loci. The nucleotide sequence of the DO beta gene is strikingly similar to that of the previously identified murine A beta 2 gene. The DO beta gene displays the same exon/intron organization as other beta genes although the fifth exon and the translated portion of the sixth exon are longer than in other genes. A striking feature of the amino acid sequence deduced from the DO beta gene sequence is the pronounced hydrophobicity of the NH2-terminal region. This feature distinguishes the putative DO beta chain from other class II beta chains and raises the possibility that DO beta chains may interact with an alpha chain that is structurally different from those of the DP, DQ, and DR loci. It further suggests that the putative DO molecule may have a function different from those of other class II antigens.

Base Sequence↗
PubMed1995

Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter.

The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but is reactivated in hepatocellular carcinoma. It has been shown that the positive and negative transcriptionally regulatory elements of the human AFP gene, which play an important role in its developmental regulation, exist over the quite extended region (4 kb). We constructed a hybrid gene consisting of herpes simplex virus thymidine kinase (HSV-tk) gene under the control of the 0.3-kb human AFP gene promoter and inserted it into a retroviral vector. When AFP-producing hepatoma cells were infected with this recombinant retrovirus (LNAF0.3TK virus), the cells expressed HSV-tk gene and exhibited increased sensitivity to ganciclovir parallel with the ability of AFP production. On the other hand, the retroviral infection had little effect on ganciclovir-mediated cytotoxicity in AFP-nonproducing hepatoma or non-hepatoma cells. Moreover, the addition of dexamethasone increased the cytotoxicity of aciclovir to the virus-infected, AFP-producing cells through a glucocorticoid-responsive element in the AFP promoter, although aciclovir, by itself, had little cytotoxicity. These results demonstrate that the AFP promoter sequence alone can provide enough tumor-specific activity for therapeutic gene expression and induce selective growth inhibition by ganciclovir in the virus-infected, AFP-producing human hepatoma cells. In addition, it is possible that expression of the therapeutic gene is modulated by administration of dexamethasone or other agents that alter AFP promoter activity after gene transduction.

3T3 Cells↗
PubMed1992

Genes, genes and more genes in the human major histocompatibility complex.

The human major histocompatibility complex (MHC), on the short arm of chromosome 6, represents one of the most extensively characterised regions of the human genome. This approximately 4 Mb segment of DNA contains genes encoding the polymorphic MHC class I and class II molecules which are involved in antigen presentation during an immune response. Recently the whole of the MHC has been cloned in cosmids and/or yeast artificial chromosomes (YACs) and large portions have been characterised for the presence of novel genes. Many unrelated genes, both housekeeping and tissue specific, have been identified and the gene density in some regions is now approaching one gene every few kilobases. Some of the novel genes encode proteins involved in the intracellular processing and transport of antigens that are presented by MHC class I molecules. Others, however, have no obvious role in the immune response. The MHC is located in the chromosome band 6p21.3 which is a Giemsa (G)-light band. The detection of such a large number of functional genes (at least 70) in this region is compatible with the idea that both housekeeping and tissue-specific genes are localised predominantly in G-light bands.

Chromosome Mapping↗
PubMed2000

Long-range interactions in neuronal gene expression: evidence from gene targeting in the GABA(A) receptor beta2-alpha6-alpha1-gamma2 subunit gene cluster.

Clustering of GABA(A) receptor alpha1, alpha6, beta2, and gamma2 subunit genes on mouse chromosome 11/human chromosome 5 may have functional significance for coordinating expression patterns, but until now there has been no evidence for cross-talk between the genes. However, altering the structure of the alpha6 gene, specifically expressed in the cerebellum, with neomycin gene insertions in two different experiments unexpectedly reduced the expression of the widespread alpha1 and beta2 genes in the forebrain. There were corresponding reductions in the levels of alpha1 and beta2 subunit proteins and in autoradiographic ligand binding densities to GABA(A) receptors in the forebrain of alpha6-/- mice. The gamma2 mRNA level was not changed, nor were beta3 and delta mRNAs. The data suggest that elements in the neo gene may have an influence over long distances in the GABA(A) subunit gene complex on as yet undefined structures coordinating the expression of the alpha1 and beta2 genes.

Animals↗
PubMed2001

Microarray-based analysis of gene expression in very large gene families: the cytochrome P450 gene superfamily of Arabidopsis thaliana.

Cytochrome P450 (P450s) are heme-thiolate protein products of a very large gene superfamily, present in all kingdoms and involved in a variety of metabolic reactions. P450s are classified according to the degree of amino acid sequence identity, with P450s of the same family defined as having >40% identity, and P450s of the same subfamily having >55% identity. Currently, 273 P450 genes distributed over 45 families have been identified in Arabidopsis, and its genome is estimated to contain as many as 286. Genome-wide DNA microarrays make it possible to broadly correlate P450 gene activity with alterations in physiological or developmental states. A potential problem with microarray research is that sequence similarity between and within these families of closely related genes may lead to cross-hybridization. We designed experiments to systematically evaluate the specificity of P450 microarrays, and showed that conditions could be optimized to provide a very high degree of hybridization specificity. Under these conditions, and employing a 20% intensity value of maximum hybridization intensity as a cut-off, labeled P450 genes exhibited essentially no cross-hybridization between families and within subfamilies. We also compared the gene transcription levels of microarray probes derived from EST clones and from genomic DNA sequences for which ESTs were not available, using cDNA produced from RNA from various Arabidopsis tissue as the target. Many of the P450 genes displayed tissue-specific expression, leading to hypotheses as to the function of individual genes and their regulation. We also observed that several of the genomic sequences reported high levels of expression, highlighting the limitations of expression analysis based on ESTs alone.

Arabidopsis↗
PubMed1989

AbrB, a regulator of gene expression in Bacillus, interacts with the transcription initiation regions of a sporulation gene and an antibiotic biosynthesis gene.

The abrB gene of Bacillus subtilis is believed to encode a repressor that controls the expression of genes involved in starvation-induced processes such as sporulation and the production of antibiotics and degradative enzymes. Two such genes, spoVG, a sporulation gene of B. subtilis, and tycA, which encodes tyrocidine synthetase I of the tyrocidine biosynthetic pathway in Bacillus brevis, are negatively regulated by abrB in B. subtilis. To examine the role of abrB in the repression of gene transcription, the AbrB protein was purified and then tested for its ability to bind to spoVG and tycA promoter DNA. In a gel mobility shift experiment, AbrB was found to bind to a DNA fragment containing the sequence from -95 to +61 of spoVG. AbrB protein exhibited reduced affinity for DNA of two mutant forms of the spoVG promoter that had been shown to be insensitive to abrB-dependent repression in vivo. These studies showed that an upstream A + T-rich sequence from -37 to -95 was required for optimal AbrB binding. AbrB protein was also observed to bind to the tycA gene within a region between the transcription start site and the tycA coding sequence as well as to a region containing the putative tycA promoter. These findings reinforce the hypothesis that AbrB represses gene expression through its direct interaction with the transcription initiation regions of genes under its control.

Amino Acid Sequence↗
PubMed1998

Identification of genes affecting lycopene formation in Escherichia coli transformed with carotenoid biosynthetic genes: candidates for early genes in isoprenoid biosynthesis.

Although isopentenyl diphosphate is a precursor of isoprenoids in Escherichia coli, the genes and enzymes involved in its biosynthesis have not been identified. Thus, we tried to isolate E. coli mutants deficient in the biosynthesis and their complementary genes by use of an artificial phenotypic screening system employing three carotenoid biosynthetic genes, crtE, crtB, and crtI. Cells were mutagenized with ethylmethanesulfonate, then transformed with a plasmid for expression of the carotenogenic genes. Mutants deficient in biosynthesis of isopentenyl diphosphate were expected to form white colonies, because they are unable to produce enough lycopene, whereas wild-type cells form red colonies. Among large numbers of red colonies, we identified 117 white colonies. Next, we transformed each mutant with an E. coli genomic library. Twenty-nine complementary genes that restore red color of host colonies were isolated. A homology search and further complementation study using subcloned genes revealed that the true complementary genes encode isopentenyl diphosphate isomerase, subunits of ATP synthase, enzymes of the Krebs cycle, some aldehyde dehydrogenases, phosphate acetyltransferase, and enzymes which relate to the biosynthesis of ubiquinones and menaquinones. Two unknown genes were also found, designated elb1 and 2, which may be involved in the early steps of isoprenoid biosynthesis.

Carotenoids↗
PubMed2001

Identification of two rodent genes encoding homologues to seminal vesicle autoantigen: a gene family including the gene for prolactin-inducible protein.

We cloned two new paralogous genes that encode proteins homologous to seminal vesicle autoantigen (SVA) in rodents. The open reading frame of one mouse gene encodes a polypeptide consisting of 151 amino acid residues which has 43% identity to SVA. RT-PCR analysis showed selective expression in the colon, and thus the protein was tentatively named "SVA-like protein in the colon (SLP-C)". The other mouse gene has an open reading frame encoding 144 amino acid residues with 46 and 65% identity to SVA and SLP-C, respectively. Expression of this gene was detected in the mammary, submaxillary, parotid, and lacrimal glands, and this protein was named "SLP in the mammary gland (SLP-M)". Orthologs of both genes were also found in rats. The three homologous genes coding for SVA, SLP-C, and SLP-M may have been generated by gene duplication with divergence of tissue expression in the course of evolution. They comprise a unique structurally-related gene family. Moreover, these genes share significant sequence homology with that of another secretory glycoprotein, prolactin-inducible protein.

Amino Acid Sequence↗
PubMed2003

Analysis of part of the chicken Rfp-Y region reveals two novel lectin genes, the first complete genomic sequence of a class I alpha-chain gene, a truncated class II beta-chain gene, and a large CR1 repeat.

The Rfp-Y region lies on the same microchromosome as the B-F/B-L region of the B complex, yet in contrast to the latter it is poorly characterised. To date it has been shown to contain at least two class I alpha-chain ( Y-F) genes, a class II B-chain gene and a C-type lectin-like gene. We describe the sequencing and analysis of some 20 kb of the Rfp-Y region, and identify several new genes. These include two novel C-type lectin-like genes ( Y-Lec1 and Y-Lec2) that differ strongly from the previously described C-type lectin-like gene found in the Rfp-Y region. We describe a complete genomic sequence of a class I alpha-chain ( Y-F) gene and its promoter from the Rfp-Y region. The predicted cDNA from this gene has high homology to the previously reported Y-F cDNAs. The promoter contains an altered enhancer A element. This portion of the Rfp-Y region also contains a truncated class II B-chain ( Y-LB) gene, as well as a large chicken repeat 1 (CR1) element.

Amino Acid Sequence↗
PubMed1990

Nucleotide sequence of the thermostable direct hemolysin gene (tdh gene) of Vibrio mimicus and its evolutionary relationship with the tdh genes of Vibrio parahaemolyticus.

The gene encoding a hemolysin similar to the thermostable direct hemolysin (TDH) of Vibrio parahaemolyticus was previously cloned from the chromosome of Vibrio mimicus. The nucleotide sequence of the hemolysin gene was determined in this study. The gene proved to be a variant of the thermostable direct hemolysin gene (tdh gene) and was designated as Vm-tdh because the sequence divergences between the Vm-tdh gene and four tdh genes of V. parahaemolyticus were 2.1-3.0%, while the sequence divergences among the four tdh genes of V. parahaemolyticus ranged between 1.4 and 3.3%. Analysis of these five tdh genes revealed that they evolved from a common ancestor in discrete and understandable order by sporadic base substitutions.

Base Sequence↗
PubMed1995

Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1.

Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related but functionally diverse peptides, encoded by separate genes and expressed in different tissues. Although the human NPY gene has been mapped to chromosome 7, we demonstrate here that the genes for human PYY and PP (PPY) are localized only 10 kb apart from each other on chromosome 17q21.1. The high degree of homology between the members of this gene family, both in primary sequence and exon/intron structure, suggests that the NPY and the PYY genes arose from an initial gene duplication event, with a subsequent tandem duplication of the PYY gene being responsible for duplication of the PYY gene being responsible for the creation of the PPY gene. A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event.

Amino Acid Sequence↗
PubMed1995

Mapping of the alpha 4 subunit gene (GABRA4) to human chromosome 4 defines an alpha 2-alpha 4-beta 1-gamma 1 gene cluster: further evidence that modern GABAA receptor gene clusters are derived from an ancestral cluster.

We demonstrated previously that an alpha 1-beta 2-gamma 2 gene cluster of the gamma-aminobutyric acid (GABAA) receptor is located on human chromosome 5q34-q35 and that an ancestral alpha-beta-gamma gene cluster probably spawned clusters on chromosomes 4, 5, and 15. Here, we report that the alpha 4 gene (GABRA4) maps to human chromosome 4p14-q12, defining a cluster comprising the alpha 2, alpha 4, beta 1, and gamma 1 genes. The existence of an alpha 2-alpha 4-beta 1-gamma 1 cluster on chromosome 4 and an alpha 1-alpha 6-beta 2-gamma 2 cluster on chromosome 5 provides further evidence that the number of ancestral GABAA receptor subunit genes has been expanded by duplication within an ancestral gene cluster. Moreover, if duplication of the alpha gene occurred before duplication of the ancestral gene cluster, then a heretofore undiscovered subtype of alpha subunit should be located on human chromosome 15q11-q13 within an alpha 5-alpha x-beta 3-gamma 3 gene cluster at the locus for Angelman and Prader-Willi syndromes.

Amino Acid Sequence↗
PubMed2003

GENIS: gene expression of sodium iodide symporter for noninvasive imaging of gene therapy vectors and quantification of gene expression in vivo.

With the goal of optimizing adenovirus-mediated suicide gene therapy for prostate cancer, we have developed a method based on the human sodium iodide symporter (hNIS) that allows for noninvasive monitoring of adenoviral vectors and quantification of gene expression magnitude and volume within the prostate. A replication-competent adenovirus (Ad5-yCD/mutTK(SR39)rep-hNIS) coexpressing a therapeutic yeast cytosine deaminase (yCD)/mutant herpes simplex virus thymidine kinase (mutTK(SR39)) fusion gene and the hNIS gene was developed. Ad5-yCD/mutTK(SR39)rep-hNIS and a replication-defective hNIS adenovirus (rAd-CMV-FLhNIS) were injected into contralateral lobes of the dog prostate and hNIS activity was monitored in live animals following administration of Na(99m)TcO(4) using gamma camera scintigraphy. Despite the close proximity of the urinary bladder, (99m)TcO(4)(-) uptake was readily detected in the prostate using viral dose levels (10(10) to 10(12) viral particles) that have been safely administered to humans. Due to its rapid clearance and short physical half-life (6 h), it was possible to obtain daily measurements of (99m)TcO(4)(-) uptake in vivo, allowing for dynamic monitoring of reporter gene expression within the prostate as well as biodistribution throughout the body. High-resolution autoradiography of prostate sections coupled with 3D reconstruction of gene expression demonstrated that the magnitude and volume of gene expression could be quantified with submillimeter resolution. Implementation of the GENIS (gene expression of Na/I symporter) technology in the clinic will facilitate optimization of future human gene therapy trials.

Adenoviridae↗
PubMed1986

The orangutan adult alpha-globin gene locus: duplicated functional genes and a newly detected member of the primate alpha-globin gene family.

We have cloned and sequenced the complete alpha 1- and alpha 2-globin genes of the orangutan, and here we compare them to the homologous genes of the human. The pattern of similarity apparent among the genes is most consistent with a model of gene correction operating on the primate alpha-globin cluster. This correction breaks down in both human and orangutan in the 3'-untranslated region at 14 base pairs downstream from the termination codon. The unit evolutionary period values calculated for either the replacement substitution or the silent substitutions are only slightly higher than the previously established molecular clock predicts. The 7-base-pair insertion in intron 2 of the human alpha 1-globin gene is not present in either orangutan gene, suggesting that this insertion is not the cause of the sequence divergence in the 3'-untranslated regions of primate alpha 2- and alpha 1-globin genes. Finally, blotting hybridization and partial DNA sequencing reveal a newly detected member of the primate alpha-globin gene family, which is located downstream from the duplicated adult alpha-globin genes.

Animals↗
PubMed1995

The human COL11A2 gene structure indicates that the gene has not evolved with the genes for the major fibrillar collagens.

The human COL11A2 gene was analyzed from two overlapping cosmid clones that were previously isolated in the course of searching the human major histocompatibility region (Janatipour, M., Naumov, Y., Ando, A., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., and Inoko, H. (1992) Immunogenetics 35, 272-278). Nucleotide sequencing defined over 28,000 base pairs of the gene. It was shown to contain 66 exons. As with most genes for fibrillar collagens, the first intron was among the largest, and the introns at the 5'-end of the gene were in general larger than the introns at the 3'-end. Analysis of the exons coding for the major triple helical domain indicated that the gene structure had not evolved with the genes for the major fibrillar collagens in that there were marked differences in the number of exons, the exon sizes, and codon usage. The gene was located close to the gene for the retinoic X receptor beta in a head-to-tail arrangement similar to that previously seen with the two mouse genes (P. Vandenberg and D. J. Prockop, submitted for publication). Also, there was marked interspecies homology in the intergenic sequences. The amino acid sequences and the pattern of charged amino acids in the major triple helix of the alpha 2(XI) chain suggested that the chain can be incorporated into the same molecule as alpha 1(XI) and alpha 1(V) chains but not into the same molecule as the alpha 3(XI)/alpha 1(II) chain. The structure of the carboxyl-terminal propeptide was similar to the carboxyl-terminal propeptides of the pro alpha 1(XI) chain and pro alpha chains of other fibrillar collagens, but it was shorter because of internal deletions of about 30 amino acids.

Amino Acid Sequence↗
PubMed1997

Molecular analysis of six dog leukocyte antigen class I sequences including three complete genes, two truncated genes and one full-length processed gene.

We have isolated six distinct dog leukocyte antigen (DLA) class I sequences. An additional functional nonclassical class I gene, DLA-79, was characterized previously. This brings the number of isolated canine class I sequences to seven. These seven loci account for nearly all class I sequences detected in genomic DNA by Southern blotting. With approximately seven members, the class I gene family in dog is considerably less complex than in either human or mouse. Three of the six sequences described in this article contain complete class I genes. These genes have the typical arrangement of exons and introns, and their predicted protein sequences have the features expected of expressed class I molecules. Two sequences contain truncated genes. These genes, having only partial class I homology and disruptive mutations, are clearly nonfunctional. The remaining locus contains a full-length processed gene which is unique among characterized class I loci. Sequence comparisons were performed to examine evolutionary relationships among the family members. Two sequences, DLA-64 (complete) and -53 (truncated), appear to be chimeras presumably formed by interlocus recombination. Using the reverse transcription-polymerase chain reaction, mRNA originating from each of the three complete genes was identified in canine peripheral blood leukocytes. DLA-79 specific transcripts were identified previously. Thus, each of the four complete canine class I genes is transcribed in vivo.

Amino Acid Sequence↗
PubMed1999

Linkage analysis of candidate genes and gene-gene interactions in chinese hypertensive sib pairs.

Previous studies of hypertension in humans and experimental animal models have identified a number of candidate genes that have since been implicated as possibly contributing to essential hypertension. Among them are the genes encoding angiotensinogen, renin, the beta- and gamma-subunits of the epithelial sodium channel (beta/gamma-ENaC), alpha-adducin, and kallikrein (KLK). To examine the role of possible contribution of these genes in ethnic Chinese, as well as the epistatic interaction among them, we studied a large cohort of hypertensive sib pairs from China. DNA samples from 310 concordant affected sibling pairs with hypertension were tested for linkage with the use of excess allele-sharing algorithms based on genotyping with highly informative GT-repeat microsatellite markers localized in the immediate vicinity of the genes encoding angiotensinogen, renin, beta- and gamma-ENaC, alpha-adducin, and KLK. Affected sib pair analysis conducted according to 3 different methods (Statistical Analysis for Genetic Epidemiology [S.A.G.E. ]/SIBPAL, MAPMAKER/SIBS, and affected pedigree member [APM] methods) revealed no evidence for linkage of any of these genes to primary hypertension in the population studied. Moreover, 2-locus sib pair linkage analyses to test for gene-gene interactions among each possible pair of candidate genes failed to yield any statistically significant results. Our findings provide no support for a significant contribution of the angiotensinogen, renin, beta/gamma-ENaC, alpha-adducin, or KLK genes, alone or in concert, to the pathogenesis of essential hypertension among Chinese. Our results emphasize the possible role of ethnic differences for complex disease genetics, as well as the need for large, well-characterized investigations.

Angiotensinogen↗
PubMed1998

Gene therapy for human colorectal carcinoma using human CEA promoter contro led bacterial ADP-ribosylating toxin genes human CEA: PEA & DTA gene transfer.

AIM:To establish a tissue-specific gene therapy for colorectal carcinoma using bacterial ADP-ribosylating toxin genes. METHODS:Pseudomonas exotoxin A domain [II+III (PEA) was cloned from genomic DNA of Pseudomonas aeruginosa.PEA and diphtheria toxin A chain gene (DTA) were modified to express eukaryotically. After sequencing, the toxin genes under the control of human carcinoembryonic antigen (CEA)promoter were cloned into retroviral vectors to construct CEAPEA and CEADTA respectively. In vitro cotransfection of the constructs with luciferase vectors and in vivo gene transfer in nude mice were subsequently carried out. RESULTS:Both CEAPEA and CEADTA specifically inhibited the reporter gene expression in the CEA positive human colorectal carcinoma (CRC) cells in vitro. Direct injection of CEAPEA and CEADTA constructs into the established human tumors in BALB/c nude mice led to significant and selective reductions in CRC tumor size as compared with that in control groups.CONCLUSION:The toxin genes, working as therapeutic genes, are suitable for the tissue-specific gene therapy for colorectal carcinoma.

Journal Article↗