PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “multigene typing”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2004

Identification of probabilistic transcriptional switches in the Ly49 gene cluster: a eukaryotic mechanism for selective gene activation.

Murine natural killer cells selectively express members of the Ly49 family of class I MHC receptors; however, the molecular mechanism controlling probabilistic expression of Ly49 proteins has not been defined. A pair of overlapping, divergent promoters discovered in the Ly49g gene functions as a molecular switch that can produce a forward transcript containing the coding region of the gene (on position) or a noncoding transcript in the opposite direction (off position), and this element maintains transcription in the chosen direction. Competition of C/EBP and TBP transcription factors for overlapping binding sites determines the relative strength of the competing promoters and the probability of transcription in a given direction. Similar elements precede all Ly49 family members, and the relative strength of the forward promoter in each inhibitory Ly49 gene correlates with the percentage of natural killer cells that express a given receptor, supporting a promoter competition model of selective gene activation.

Animals↗
PubMed1986

Gene reorganization during serial divisions of normal human cells.

We have followed during serial divisions of human fibroblasts the presence in chromosomal and extrachromosomal DNA, of two genes that are expressed in fibroblasts, actin and interferon, and of one that is not expressed, globin. The intensity of the blot hybridization of the actin and globin probes with chromosomal DNA diminished during serial divisions of diploid fibroblasts. The interferon gene remained constant throughout the human fibroblast life span. Chromosomal DNA sequences were present in extrachromosomal circular DNA which appeared at the end of the fibroblast life span. The results could explain some functional changes that occur in these cell populations when their division potential declines.

Actins↗
PubMed1998

Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies.

The early growth response 2 gene (EGR2) is part of a multigene family encoding Cys2His2 type zinc-finger proteins and may play a role in the regulation of cellular proliferation. Egr2, (also known as Krox20) is the mouse orthologue of human EGR2 and was first identified as an immediate-early response gene, encoding a protein that binds DNA in a sequence-specific manner and acts as a transcription factor. Stable expression of Egr2 is specifically associated with the onset of myelination in the peripheral nervous system (PNS). Egr2(-/-) mice display disrupted hindbrain segmentation and development, and a block of Schwann-cell differentiation at an early stage. We hypothesized that Egr2 may be a transcription factor affecting late myelin genes and that human myelinopathies of the PNS may result from mutations in EGR2. In support of this hypothesis, we have identified one recessive and two dominant missense mutations in EGR2 (within regions encoding conserved functional domains) in patients with congenital hypomyelinating neuropathy (CHN) and a family with Charcot-Marie-Tooth type 1 (CMT1).

Adolescent↗
PubMed2001

Identification of genes encoding adenylate isopentenyltransferase, a cytokinin biosynthesis enzyme, in Arabidopsis thaliana.

The initial step in the de novo biosynthesis of cytokinin in higher plants is the formation of isopentenyladenosine 5'-monophosphate (iPMP) from AMP and dimethylallylpyrophosphate (DMAPP), which is catalyzed by adenylate isopentenyltransferase (IPT). Although cytokinin is an essential hormone for growth and development, the nature of the enzyme for its biosynthesis in higher plants has not been identified. Herein, we describe the molecular cloning and biochemical identification of IPTs from Arabidopsis thaliana. Eight cDNAs encoding putative IPT, designated as AtIPT1 to AtIPT8, were picked up from A. thaliana. The Escherichia coli transformants expressing the recombinant proteins excreted cytokinin species into the culture medium except for that expressing AtIPT2 that is a putative tRNA IPT. A purified recombinant AtIPT1 catalyzed the formation of iPMP from DMAPP and AMP. These results indicate that the small multigene family contains both types of isopentenyltransferase, which could synthesize cytokinin and mature tRNA.

Alkyl and Aryl Transferases↗
PubMed1996

Correlation of genetic and physical maps at the A mating-type locus of Coprinus cinereus.

The A mating type locus of Coprinus cinereus is remarkable for its extreme diversity, with over 100 different alleles in natural populations. Classical genetic studies have demonstrated that this hypervariability arises in part from recombination between two subloci of A, alpha and beta, although more recent population genetic data have indicated a third segregating sublocus. In this study, we characterized the molecular basis by which recombination generates nonparental A mating types. We mapped the frequency and location of all recombination events in two crosses and correlated the genetic and physical maps of A. We found that all recombination events were located in 6 kb of noncoding DNA between the alpha and beta subloci and that the rate of recombination in this noncoding region matched that generally observed for this genome. No recombination within gene clusters or within coding regions was observed, and the two alpha and beta subloci described in genetic analyses correlated with the previously characterized alpha and beta gene clusters. We propose that pairs of genes constitute both the sex determining and the hereditary unit of A.

Chromosome Mapping↗
PubMedDate not supplied

Chromosomal localization of omega and trophoblast interferon genes in goat and sheep by fluorescent in situ hybridization.

Fluorescent in situ hybridization (FISH) of the cattle cDNA probe bTP-509 to goat (Capra hircus L.) and sheep (Ovis aries L.) R-banded metaphase chromosomes localized the omega (IFNW) and trophoblast (IFNT) interferon genes to goat chromosome 8q15 and sheep chromosome 2p15. Caprine chromosome 8 and ovine chromosome 2p are equivalent in banding pattern to cattle chromosome 8. Since FISH has previously localized IFNW and IFNT genes to cattle chromosome 8q15 and river buffalo 3q15, the localization of IFNW and IFNT genes in goat and sheep provides evidence in support of the hypothesis that chromosome-banding homology among these four species is indicative of underlying genetic homology.

Animals↗
PubMed1999

Activation of silent replication origins at autonomously replicating sequence elements near the HML locus in budding yeast.

In the budding yeast, Saccharomyces cerevisiae, replicators can function outside the chromosome as autonomously replicating sequence (ARS) elements; however, within chromosome III, certain ARSs near the transcriptionally silent HML locus show no replication origin activity. Two of these ARSs comprise the transcriptional silencers E (ARS301) and I (ARS302). Another, ARS303, resides between HML and the CHA1 gene, and its function is not known. Here we further localized and characterized ARS303 and in the process discovered a new ARS, ARS320. Both ARS303 and ARS320 are competent as chromosomal replication origins since origin activity was seen when they were inserted at a different position in chromosome III. However, at their native locations, where the two ARSs are in a cluster with ARS302, the I silencer, no replication origin activity was detected regardless of yeast mating type, special growth conditions that induce the transcriptionally repressed CHA1 gene, trans-acting mutations that abrogate transcriptional silencing at HML (sir3, orc5), or cis-acting mutations that delete the E and I silencers containing ARS elements. These results suggest that, for the HML ARS cluster (ARS303, ARS320, and ARS302), inactivity of origins is independent of local transcriptional silencing, even though origins and silencers share key cis- and trans-acting components. Surprisingly, deletion of active replication origins located 25 kb (ORI305) and 59 kb (ORI306) away led to detection of replication origin function at the HML ARS cluster, as well as at ARS301, the E silencer. Thus, replication origin silencing at HML ARSs is mediated by active replication origins residing at long distances from HML in the chromosome. The distal active origins are known to fire early in S phase, and we propose that their inactivation delays replication fork arrival at HML, providing additional time for HML ARSs to fire as origins.

Base Sequence↗
PubMed1988

Somatic cell mapping and restriction fragment analysis of bovine alpha and beta interferon gene families.

DNA from bovine x hamster hybrid cells preferentially segregating bovine chromosomes has been analyzed by blot hybridization with alpha and beta interferon probes. Retention or loss of bovine interferon genes was compared to segregation of bovine isozyme loci representing previously described syntenic groups. Families of bovine alpha (IFNA) and beta (IFNB) interferon genes were segregated in concordance with each other and with aconitase-1 (ACO1) on bovine syntenic group U18. This syntenic relationship is conserved on human chromosome 9p and on the portion of mouse chromosome 4 proximal to the centromere. In addition, cattle restriction fragment length polymorphisms were identified with both IFNA and IFNB probes. Of particular interest is a polymorphism apparently due to duplication of IFNB genes.

Animals↗
PubMed2006

Meta- and reanalysis of gene expression profiles of hot and cold thyroid nodules and papillary thyroid carcinoma for gene groups.

CONTEXT: There are an increasing number of studies analyzing gene expression profiles in various benign and malignant thyroid tumors. This creates the opportunity to validate results obtained from one microarray study with those from other data sets. This process requires rigorous methods for accurate comparison. OBJECTIVE: The ability to compare data sets derived from different Affymetrix GeneChip generations and the influence of intra- and interindividual comparisons of gene expression data were evaluated to build multigene classifiers of benign thyroid nodules to verify a previously proposed papillary thyroid carcinoma (PTC) classifier and to look for molecular pathways essential for PTC oncogenesis. METHODS: Gene expression profile data sets from autonomously functioning and cold thyroid nodules and from PTC were analyzed by support vector machines. GenMAPP analysis was used for PTC data analysis to examine the expression patterns of biologically relevant gene sets. RESULTS: Only intraindividual reference samples allowed the identification of subtle changes in the expression patterns of relevant signaling cascades, such as the MAPK pathway in PTC. Using an artificial intelligence approach, the autonomously functioning and cold thyroid nodule multigene classifiers were derived and evaluated by cross-comparisons. CONCLUSION: We recommend defining classifiers within one generation of gene chips and subsequently checking them across different array generations. Using this approach, we have demonstrated the specificity of a previously reported PTC classifier on an independent collection of benign tumors. Moreover, we propose multigene classifiers for different types of benign thyroid nodules.

Algorithms↗
PubMed2003

Acquisition of MHC-specific receptors on murine natural killer cells.

NK cells in adult mice express two families of MHC class I-specific receptors, namely, Ly49 and CD94/NKG2. Co-expression of these receptors in various combinations generates diverse receptor repertoires. The expression of individual receptors is mostly stochastic and independent of each other. NK cells acquire the receptors as they develop from progenitors in the bone marrow in adult mice. In vivo as well as in vitro studies have shown that the acquisition of the receptors is ordered and regulated by the host MHC class I. Developing NK cells first acquire CD94/NKG2 and subsequently various Ly49 receptors in an ordered manner. Unlike adult NK cells, most fetal and neonatal NK cells express CD94/NKG2 but not Ly49. During the first several weeks after birth, NK cells expressing various Ly49 receptors slowly accumulate, while CD94/NKG2+ NK cells decrease to approximately 50% of the population. The acquisition of NK receptors following hematopoietic stem cell transplantation is also a slow and apparently preprogrammed process, mimicking the ontogeny, regardless of whether stem cells from fetal liver or adult bone marrow are used as donors. The regulation of the transcription of individual receptor genes is rather complex, since two promoters have been identified for the genes encoding Ly49 and CD94.

Animals↗
PubMed2001

Clonotypic structure of the human CD4+ memory T cell response to cytomegalovirus.

High steady-state frequencies of CMV-specific CD4(+) memory T cells are maintained in CMV-exposed subjects, and these cells are thought to play a key role in the immunologic control of this permanent infection. However, the essential components of this response are poorly defined. Here, we report the use of a step-wise application of flow cytometric and molecular techniques to determine the number and size of the TCR Vbeta-defined clonotypes within freshly obtained CMV-specific CD4(+) memory T cell populations of four healthy, CMV-exposed human subjects. This analysis revealed a stable clonotypic hierarchy in which 1-3 dominant clonotypes are maintained in concert with more numerous subdominant and minor clonotypes. These dominant clonotypes accounted for 10-50% of the overall CMV response, and comprised from 0.3 to 4.0% of peripheral blood CD4(+) T cells. Two subjects displayed immunodominant responses to single epitopes within the CMV matrix phosphoprotein pp65; these single epitope responses were mediated by a single dominant clonotype in one subject, and by multiple subdominant and minor clonotypes in the other. Thus, the CMV-specific CD4(+) T cell memory repertoire in normal subjects is characterized by striking clonotypic dominance and the potential for epitope focusing, suggesting that primary responsibility for immunosurveillance against CMV reactivation rests with a handful of clones recognizing a limited array of CMV determinants. These data have important implications for the understanding of mechanisms by which a genetically stable chronic viral pathogen such as CMV is controlled, and offer possible insight into the failure of such control for a genetically flexible pathogen like HIV-1.

Antigens, CD↗
PubMed2000

Biotin carboxyl carrier protein isoforms in Brassicaceae oilseeds.

De novo fatty acid biosynthesis occurs predominantly in plastids. The committed step for this pathway is the production of malonyl-CoA catalysed by acetyl-CoA carboxylase (ACCase). In most plants, plastidial ACCase is a multisubunit complex minimally comprised of four polypeptides, which catalyse two reactions. In the simple oilseed plant, Arabidopsis thaliana, two cDNAs encoding biotin carboxyl carrier protein (BCCP) isoforms have been identified. The remaining three subunits of ACCase appear to be single gene members in A. thaliana [Mekhedov, Martinez de Ilarduya and Ohlrogge (2000) Plant Physiol. 122, 389-401]. Transcript and protein analyses indicate that BCCP isoform 1 is constitutively expressed while isoform 2 is predominantly expressed in developing seeds. The apparent masses of constitutive and seed-enriched BCCP isoforms agree with the apparent masses of recombinantly expressed isoforms 1 and 2, respectively. In a related oilseed, Brassica napus, multiple putative BCCP polypeptides were also observed in developing seeds. The presence of a divergent class of BCCP genes in A. thaliana and B. napus, coincident with appropriately sized biotin-containing proteins expressed specifically in developing seeds, suggests that these BCCPs play an evolutionarily conserved role in oil deposition.

Acetyl-CoA Carboxylase↗
PubMed1987

[Effect of promoter duplication in the synthetic interferon gene on the level of its expression].

The expression of the artificial gene for the human leukocyte interferon (IFN) synthesized by the chemo-enzymic method has been studied in Escherichia coli cells. The genetic constructions in which the IFN gene transcription is carried out from A2 and B promoters of T7 phage or from E. coli lacZ UV5 gene promoter have been obtained, based on pEMB101 plasmid. In addition, the level of interferon production, depending on the promoter used, has been studied. It has been shown that the tandemly located promoters increase efficiency of the IFN gene expression.

DNA Restriction Enzymes↗
PubMed1987

[Duplication of a synthetic gene for human leukocyte interferon and its expression in polycistron mRNA with coupled translation system].

Using a chemically synthesised adapter, the coding part of an artificial gene for human leukocyte alpha 2 interferon (ifn-alpha 2) has been duplicated. The adapter contained a termination signal of the first gene (TAA) within the Shine-Dalgarno sequence of the second gene (TAAGGA), distance between the terminating codon and starting codon of the second gene being 11 nucleotides. In another case this distance was 69 nucleotides, with the same SD sequence. The expression of the tandems as a part of polycistrons has been studied under control of promoters Plac, (Ptrp)2 of E. coli, and PVIII of M13 phage. It was found that tandems of ifn-alpha 2 genes in polycistronic structures trp L-ifn-ifn and IX-VIII-ifn-ifn under control of promoters (Ptrp)2 and PVIII, respectively, provided high level of the interferon biosynthesis, thus differing from the tandem under Plac promoter control, which had only ifn-ifn translation coupling.

Escherichia coli↗
PubMed1993

Cytoskeletal architecture and epithelial differentiation: molecular determinants of cell interaction and cytoskeletal filament anchorage.

Desmosomes are morphologically well defined junctions between epithelial cells and also some other cells such as myocardiocytes, meningeal cells and dendritic reticulum cells of lymphatic follicles. Besides their function in cell coupling, desmosomes anchor components of the cytoskeleton, i.e. intermediate-sized filaments (IFs), through their cytoplasmic plaques, thereby contributing to cytoskeletal and tissue architecture. In molecular terms, desmosomes are specific assemblies of transmembrane glycoproteins of the cadherin family, desmoglein(s) and desmocollin(s), that contribute to cell adhesion via their extracellular, aminoterminal domains and to plaque formation and IF coupling through their cytoplasmic, carboxyterminal "tails". Using transfection assays, we analyzed the function of different tail domains in plaque assembly and IF anchorage. Furthermore, we present evidence that both desmogleins and desmocollins represent multigene subfamilies showing cell type specific expression and that a desmosomal plaque protein occurring in stratified and complex epithelia, the "band 6 protein", is related to the plakoglobin family.

Cadherins↗
PubMed1994

A common region of homozygous deletion in malignant human gliomas lies between the IFN alpha/omega gene cluster and the D9S171 locus.

Deletions of the 9p-localized type-I interferon (IFN) genes and adjacent loci often occur during the development of malignant glioma. We have applied restriction fragment length polymorphism and microsatellite analysis to 12 loci covering this region of 9p and 3 loci on 9q in 74 human glial tumor tissues to define and further localize the smallest region of hemizygous or homozygous deletion common to the tumors. Three regions of homozygous deletion were evident among the panel of tumors; only one of these, however, residing between D9S171 and the IFN alpha/omega gene cluster, was involved in multiple cases (13 glioblastomas). Hemizygous deletion of this same region was observed in an additional 27 tumors. In total these data indicate the frequent inactivation of a novel tumor suppressor gene residing adjacent to and centromeric of the type-I IFN genes in malignant gliomas.

Alleles↗
PubMed2002

Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system.

The human kallikreins are a large multigene family of closely related serine-type proteases. In this regard, they are similar to the multigene kallikrein families characterized in mice and rats. There is a much more extensive body of knowledge regarding the function of mouse and rat kallikreins in comparison with the human kallikreins. Human kallikrein 6 has been proposed as the homologue to rat myelencephalon-specific protease, an arginine-specific degradative-type protease abundantly expressed in the central nervous system and implicated in demyelinating disease. We present the x-ray crystal structure of mature, active recombinant human kallikrein 6 at 1.75-A resolution. This high resolution model provides the first three-dimensional view of one of the human kallikreins and one of only a few structures of serine proteases predominantly expressed in the central nervous system. Enzymatic data are presented that support the identification of human kallikrein 6 as the functional homologue of rat myelencephalon-specific protease and are corroborated by a molecular phylogenetic analysis. Furthermore, the x-ray data provide support for the characterization of human kallikrein 6 as a degradative protease with structural features more similar to trypsin than the regulatory kallikreins.

Amino Acid Sequence↗