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Results for “gene expression variability”

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At least 163 records · Page 9Linked to original sources
PubMed2003

T-cell receptor variable gamma chain gene expression in the interaction between rat gammadelta-type T cells and heat-shock protein 70-like molecule.

We previously reported that rat T-cell receptor (TCR) Vdelta6 of T-cell hybridomas was preferentially involved in recognition of the cell surface-expressed 70 kDa rat heat-shock cognate (hsc70, a constitutively expressed member of the hsp 70 family) protein-like molecule (#067 molecule). In the present study, we analyzed usage of the TCR Vgamma family of #067-restricted T-cell hybridomas. Our data indicated that most of these hybridomas expressed transcripts of TCR Vgamma1 and/or Vgamma2. However, some of the Vgamma2 transcripts were out-of-frame, suggesting that the TCR Vgamma1 family may be important for the recognition of #067-defined molecules. TCR Vgamma1 transcripts were detected in not only #067-restricted T-cell hybridomas, but #067-non restricted ones as well. However, V-J nucleotide sequences of #067-restricted and #067-non restricted T-cell hybridomas suggested that #067-restricted T-cell hybridomas showed limited insertion of nucleotide stretch as compared with #067-non restricted ones. In terms of amino acids, only one amino acid was added in #067-restricted T-cell hybridomas, whereas two or three amino acids were added in #067-non restricted ones. These data suggest that the heterodimer of the TCR relatively short stretch form of Vgamma1 molecule and TCR Vdelta6 may participate in recognition of the #067 molecule.

Animals↗
PubMed1996

Temporal Variability in Nitrogenase Gene Expression in Natural Populations of the Marine Cyanobacterium Trichodesmium thiebautii.

We report a distinct diel periodicity in the abundance of nifH (dinitrogenase reductase) mRNA in natural populations of the nonheterocystous marine cyanobacterium Trichodesmium thiebautii. Our observations show that in addition to translational and posttranslational controls, Trichodesmium nitrogenase expression is also regulated at the transcriptional and/or posttranscriptional level.

Journal Article↗
PubMed2000

Localized reversible frameshift mutation in the flhA gene confers phase variability to flagellin gene expression in Campylobacter coli.

Phase variation of flagellin gene expression in Campylobacter coli UA585 was correlated with high-frequency, reversible insertion and deletion frameshift mutations in a short homopolymeric tract of thymine residues located in the N-terminal coding region of the flhA gene. Mutation-based phase variation in flhA may generate functional diversity in the host and environment.

Bacterial Proteins↗
PubMed2005

Sequence variability, gene structure, and expression of full-length human endogenous retrovirus H.

Recently, we identified and classified 926 human endogenous retrovirus H (HERV-H)-like proviruses in the human genome. In this paper, we used the information to, in silico, reconstruct a putative ancestral HERV-H. A calculated consensus sequence was nearly open in all genes. A few manual adjustments resulted in a putative 9-kb HERV-H provirus with open reading frames (ORFs) in gag, pro, pol, and env. Long terminal repeats (LTRs) differed by 1.1%, indicating proximity to an integration event. The gag ORF was extended upstream of the normal myristylation start site. There was a long leader (including a "pre-gag" ORF) region positioned like the N terminus of murine leukemia virus (MLV) "glyco-Gag," potentially encoding a proline- and serine-rich domain remotely similar to MLV pp12. Another ORF, starting inside the 5' LTR, had no obvious similarity to known protein domains. Unlike other hitherto described gammaretroviruses, the reconstructed Gag had two zinc finger motifs. Alternative splicing of sequences related to the HERV-H consensus was confirmed using dbEST data. env transcripts were most prevalent in colon tumors, but also in normal testis. We found no evidence for full length env transcripts in the dbEST. HERV-H had a markedly skewed nucleotide composition, disfavoring guanine and favoring cytidine. We conclude that the HERV-H consensus shared a gene arrangement common to gammaretroviruses with gag separated by stop codon from pro-pol in the same reading frame, while env resides in another reading frame. There was also alternative splicing. HERV-H consensus yielded new insights in gammaretroviral evolution and will be useful as a model in studies on expression and function.

Amino Acid Sequence↗
PubMed1994

Predominant TCR-alpha beta variable and joining gene expression by muscle-infiltrating lymphocytes in the idiopathic inflammatory myopathies.

The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases in which autoreactive T cells are thought to play a pathogenetic role. We have determined the pattern of TCR-alpha beta gene expression by muscle-infiltrating lymphocytes within clinically and serologically defined groups of IIM patients. We utilized the PCR to study TCR V gene expression in muscle biopsies from nine polymyositis (PM) and eight dermatomyositis (DM) patients, all of whom had autoantibodies directed against histidyl-transfer RNA synthetase (anti-Jo-1 autoantibodies). While the TCR repertoire in DM patients was generally polyclonal, an oligoclonal profile characterized PM patients. Certain V gene families were predominantly expressed; V alpha 1 and V beta 6 gene families were detected in 82 and 91% of PM biopsies, respectively. TCR expression was characterized further by analyzing J gene usage from four PM patients expressing the V beta 6 gene. Sequence analysis of 40 independent recombinants (10 per patient) identified only seven V beta 6 clonotypes and restricted usage of the related J beta 2.1, -2.3, and -2.7 genes. These data, describing predominant TCR V and J gene usage by muscle-infiltrating lymphocytes in myositis patients, suggest that Ag-driven T cell responses may play a primary role in mediating some forms of the IIM.

Adult↗
PubMed1993

Diversity of immunoglobulin light chain usage in the human immune response to Haemophilus influenzae type b capsular polysaccharide.

The response to the capsular polysaccharide of Haemophilus influenzae type b (Hib PS) has been used to determine the molecular basis of antibody gene diversity in humans. In contrast to the relatively restricted nature of anti-Hib PS heavy-chain variable region gene expression, a variety of light-chain variable region genes may encode this antibody (Ab) response. Light-chain variable region gene usage appears to determine the expression of certain Ab idiotypes and fine antigen specificity. To further define the role of light-chain variable region gene usage in important anti-Hib PS Ab subgroups, we have cloned and sequenced a number of immunoglobulin light-chain variable region genes (IgVL) from human monoclonal IgA anti-Hib PS Ab generated in response to Hib PS-protein conjugate vaccines. Three of these Ab are encoded by unusual variable segments. One kappa-Ab is encoded by the "predominant" V kappa II A2 germline gene but, in contrast to a previously reported A2-encoded IgVL sequence, differs from the A2 germline sequence. The IgVL sequence of a second Ab is the only sequence of a kappa-Ab that cross-reacts with the structurally related antigen Escherichia coli K100 polysaccharide reported to date. This IgVL is encoded by a V kappa III-segment most closely homologous to the Humhv328/L16 germline gene, whereas previous reports suggested V kappa III-encoded anti-Hib PS Ab might be exclusively encoded by the germline gene Humhv325/A27.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Altered growth and phenotype in clonal mycN transfectants of the SK-N-SH neuroblastoma cell line.

We have attempted to distinguish in human neuroblastoma between the effects of mycN on differentiation and its potential to promote malignant progression. Others have observed out-growth of autocrine cells with evidence of an advanced malignant phenotype in a mycN-transfected clonal cell line derived from the single-copy mycN neuroblastoma, SK-N-SH. We have now transfected the parental cell line with the same mycN expression vector and selected 5 clones characterized by unique and stable chromosomal integration sites and variable exogenous copy numbers. mycN gene expression was variable in the different clones and correlated roughly with the copy number of transfected mycN genes. Clones with minimal levels of mycN gene expression had a neuroblastic phenotype and low numbers of surface HLA class-I molecules. Clones with high levels of mycN expression had a Schwann/glial-like phenotype with higher surface HLA class-I display without imbalance of expression of specific loci and accelerated growth. Two such clones were capable of anchorage-independent growth in the absence of serum, and acquired tumorigenic properties. Our results show that exogenous mycN expression can be associated with a differentiation of neuroblastoma cells along the Schwann/glial pathway and can induce accelerated and autonomous growth.

Animals↗
PubMed2002

Control genes and variability: absence of ubiquitous reference transcripts in diverse mammalian expression studies.

Control genes, commonly defined as genes that are ubiquitously expressed at stable levels in different biological contexts, have been used to standardize quantitative expression studies for more than 25 yr. We analyzed a group of large mammalian microarray datasets including the NCI60 cancer cell line panel, a leukemia tumor panel, and a phorbol ester induction time course as well as human and mouse tissue panels. Twelve housekeeping genes commonly used as controls in classical expression studies (including GAPD, ACTB, B2M, TUBA, G6PD, LDHA, and HPRT) show considerable variability of expression both within and across microarray datasets. Although we can identify genes with lower variability within individual datasets by heuristic filtering, such genes invariably show different expression levels when compared across other microarray datasets. We confirm these results with an analysis of variance in a controlled mouse dataset, showing the extent of variability in gene expression across tissues. The results show the problems inherent in the classical use of control genes in estimating gene expression levels in different mammalian cell contexts, and highlight the importance of controlled study design in the construction of microarray experiments.

Animals↗
PubMed1999

Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas.

The many binding studies of monoclonal immunoglobulin (Ig) produced by plasmacytomas have found no universally common binding properties, but instead, groups of plasmacytomas with specific antigen-binding activities to haptens such as phosphorylcholine, dextrans, fructofuranans, or dinitrophenyl. Subsequently, it was found that plasmacytomas with similar binding chain specificities not only expressed the same idiotype, but rearranged the same light (V(L)) and heavy (V(H)) variable region genes to express a characteristic monoclonal antibody. In this study, we have examined by enzyme-linked immunosorbent assay five antibodies secreted by silicone-induced mouse plasmacytomas using a broader panel of antigens including actin, myosin, tubulin, single-stranded DNA, and double-stranded DNA. We have determined the Ig heavy and light chain V gene usage in these same plasmacytomas at the DNA and RNA level. Our studies reveal: (a) antibodies secreted by plasmacytomas bind to different antigens in a manner similar to that observed for natural autoantibodies; (b) the expressed Ig heavy genes are restricted in V gene usage to the V(H)-J558 family; and (c) secondary rearrangements occur at the light chain level with at least three plasmacytomas expressing both kappa and lambda light chain genes. These results suggest that plasmacytomas use a restricted population of B cells that may still be undergoing rearrangement, thereby bypassing the allelic exclusion normally associated with expression of antibody genes.

Amino Acid Sequence↗
PubMed1992

Variables affecting antisense RNA inhibition of gene expression.

We have sought to determine what variables affect the extent of inhibition of gene expression by stable nuclear-derived antisense RNAs. Myosin heavy chain gene II (MHCII) expression in Dictyostelium was used as a model system, because previous results have shown that nearly complete inhibition of expression can be achieved under appropriate conditions. Various fragments of the myosin gene were inserted into several transformation vectors in both sense and antisense orientation, and the effects on expression of protein and RNA from the endogenous MHC II gene were assayed. The results indicate that the critical factor was the particular fragment of the gene used to produce the antisense RNA. Some fragments produced complete inhibition of expression, whereas others gave only slight inhibition. The fragments that produced the greatest inhibition were from the tail region of the gene. In addition, cells were capable of overcoming the inhibition while still expressing the antisense RNA. We hypothesize that the three-dimensional topology of the antisense and sense RNAs determines their accessibility for interstrand hybridization. Transformation with sense fragments of the myosin gene also caused inhibition of the endogenous myosin gene. The inhibition seen with sense expression is not as dramatic as that for antisense, but it had the same phenotypic consequences for the cells. This phenomenon, which has now been documented in other systems, may be mechanistically similar to inhibition by antisense RNA in our system.

Animals↗
PubMed1984

Immunologic memory to phosphocholine. IV. Hybridomas representative of Group I (T15-like) and Group II (non-T15-like) antibodies utilize distinct VH genes.

The anti-phosphocholine (PC) memory response elicited in BALB/c mice by phosphocholine-keyhole limpet hemocyanin (PC-KLH) contains two groups of antibodies distinguished by their fine specificity for PC and p-nitrophenylphosphocholine (NPPC). Group I antibodies are inhibited by both PC and NPPC, while Group II antibodies are inhibited appreciably only by NPPC; only Group I antibodies are dominated by the T15 idiotype. Anti-PC hybridomas representative of the memory response to PC-KLH were produced to examine the variable region genes expressed by memory B cells. Two IgM hybridomas were of the Group I type, because they were inhibited by both PC and NPPC and they bound to the pneumococcus R36A. However, only one of these antibodies (PCM-2) expressed a T15 idiotope, while the other (PCM-1) did not express any of three T15 idiotopes. Despite its negative T15 idiotype profile, N-terminal amino acid sequencing of PCM-1 purified heavy chain and Southern blots of the hybridoma DNA indicated that it utilizes the T15 VH and JH1 genes. Three hybridomas, IgG1, IgM, and IgE, typical of Group II antibodies, were examined; these were negative for three T15 idiotopes and displayed measurable avidity only for NPPC in a PC-protein binding inhibition assay. These three hybridoma antibodies, like serum Group II IgG1, did not measurably bind to the bacterium R36A. The heavy chain amino termini of all three of these antibodies were inaccessible for Edman degradation. Southern blots of DNA from the IgG1 hybridoma revealed the T15 VH gene to be in the germ line configuration only and unassociated with any JH segment, indicating that this Group II antibody utilizes a VH gene different from the T15 family. These results signify that, whereas some diversity of the (anti-PC) memory response may be generated by somatic diversification of variable regions important in the primary response, a significant contribution to the overall heterogeneity of memory antibodies originates in the expression of additional variable region genes.

Amino Acid Sequence↗
PubMed1986

Diversity, rearrangement, and expression of murine T cell gamma genes.

Although the T cell gamma genes are similar in many respects to T cell receptor alpha and beta genes, earlier studies suggested that only a single gamma variable (V gamma) gene is expressed in mature T cells. We report the isolation and characterization of three new rearranged V gamma genes from murine fetal thymocytes. Although each of the new V gamma gene rearrangements is present in fetal thymocytes, two of them are undetectable in mature T cells. The levels of mRNA corresponding to each type of V gamma gene rearrangement in mature T cells are dramatically diminished compared with those in fetal thymocytes, although the abundance of two of the rearranged genes is increased in mature T cells. Our results demonstrate that there is significant expressed variability of gamma genes in immature T cells. Furthermore, the dynamics of gamma gene rearrangement and expression support the idea that gamma genes function in immature T cells.

Animals↗
PubMed2004

A database for management of gene expression data in situ.

MOTIVATION: To create a spatiotemporal atlas of Drosophila segmentation gene expression at cellular resolution. RESULTS: The expression of segmentation genes plays a crucial role in the establishment of the Drosophila body plan. Using the IBM DB2 Relational Database Management System we have designed and implemented the FlyEx database. FlyEx contains 2832 images of 14 segmentation gene expression patterns obtained from 954 embryos and 2,073,662 quantitative data records. The averaged data is available for most of segmentation genes at eight time points. FlyEx supports operations on images of gene expression patterns. The database can be used to examine the quality of data, analyze the dynamics of formation of segmentation gene expression domains, as well as estimate the variability of gene expression patterns. We also provide the capability to download data of interest. AVAILABILITY: http://urchin.spbcas.ru/flyex, http://flyex.ams.sunysb.edu/flyex

Animals↗
PubMed2006

Phenotypic consequences of promoter-mediated transcriptional noise.

A more complete understanding of the causes and effects of cell-cell variability in gene expression is needed to elucidate whether the resulting phenotypes are disadvantageous or confer some adaptive advantage. Here we show that increased variability in gene expression, affected by the sequence of the TATA box, can be beneficial after an acute change in environmental conditions. We rationally introduce mutations within the TATA region of an engineered Saccharomyces cerevisiae GAL1 promoter and measure promoter responses that can be characterized as being either highly variable and rapid or steady and slow. We computationally illustrate how a stable transcription scaffold can result in "bursts" of gene expression, enabling rapid individual cell responses in the transient and increased cell-cell variability at steady state. We experimentally verify computational predictions that the rapid response and increased cell-cell variability enabled by TATA-containing promoters confer a clear benefit in the face of an acute environmental stress.

Base Sequence↗
PubMed2006

A sequence-oriented comparison of gene expression measurements across different hybridization-based technologies.

Over the last decade, gene expression microarrays have had a profound impact on biomedical research. The diversity of platforms and analytical methods available to researchers have made the comparison of data from multiple platforms challenging. In this study, we describe a framework for comparisons across platforms and laboratories. We have attempted to include nearly all the available commercial and 'in-house' platforms. Using probe sequences matched at the exon level improved consistency of measurements across the different microarray platforms compared to annotation-based matches. Generally, consistency was good for highly expressed genes, and variable for genes with lower expression values as confirmed by quantitative real-time (QRT)-PCR. Concordance of measurements was higher between laboratories on the same platform than across platforms. We demonstrate that, after stringent preprocessing, commercial arrays were more consistent than in-house arrays, and by most measures, one-dye platforms were more consistent than two-dye platforms.

Chromosome Mapping↗
PubMed2000

Analysis of the expressed immunoglobulin variable region heavy chain gene products in paraproteins from Iranian patients with multiple myeloma.

The frequency of expression of immunoglobulin (Ig) variable region heavy (VH ) chain gene products was studied in 43 Iranian patients with mutiple myeloma (MM). The expressed VH gene families and associated cross-reactive idiotypes (CRI) were analysed by immunoblotting and ELISA, using peptide-induced polyclonal antibodies specific for VH 1-VH 6 gene families and monoclonal antibodies (MAb) recognising CRI linked to theVH 1, VH 3, VH 4 and VH 6 gene families. The results revealed that the VH 3 family (60. 5%) was the most predominant gene family. In contrast, no paraproteins were encoded by genes from the VH 2 gene family and only 2.3% were encoded by the VH 5 family. The panel of paraproteins tested rarely expressed the probed VH -associated CRI. Our results suggest that: 1-The Ig VH genes, may not be randomly expressed in the malignant plasma cells from Iranian patients with MM. 2- Some of the genes seem to be negatively selected or highly mutated, as evidenced by the lack of expression of the probed CRI.

Blotting, Western↗