Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “coding change”

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 1,405 records · Page 78Linked to original sources
PubMed2000

Genomic instability in multistage carcinogenesis.

For a normal cell to accumulate multiple genetic changes during multistage carcinogenesis, the induction of genomic instability is considered advantageous. Since most human cancers are associated with exposure to environmental carcinogens, it is likely that environmental carcinogens interact with genomic instability. Our results indeed suggest that carcinogens contribute to the induction of microsatellite instability and induce more mutations in those cells which show microsatellite instability. We have recently developed a sensitive method to clearly detect changes in simple repeats of coding sequences of cancer genes and the results suggest that such sequences of different genes are mutated in different tumors.

Animals↗
PubMed2002

Expression of IL-17B in neurons and evaluation of its possible role in the chromosome 5q-linked form of Charcot-Marie-Tooth disease.

IL-17B is a recently identified homolog of IL-17. Northern analysis revealed that IL-17B mRNA is expressed at very high levels in spinal cord and at much lower and more variable levels in trachea, prostate, lung, small intestine, testes, adrenal, and pancreas. In developing mouse embryos IL-17B expression was first detected at day 11 and appeared to peak at day 15. In situ analysis of mouse spinal cord, dorsal root ganglia, and brain demonstrated that IL-17B mRNA is primarily expressed by the neurons. Immunohistochemical analysis of human spinal cord, dorsal root ganglia, cerebral cortex, cerebellum, and hippocampus demonstrated that IL-17B protein is primarily localized to the neuronal cell bodies and axons. Radiation hybrid mapping localized the IL-17B gene to a region on human chromosome 5q that is associated with a rare autosomal recessive form of Charcot-Marie-Tooth demyelinating disease. However, no changes were found in the coding regions, splice junctions, intron 1, or the 5' and 3' untranslated regions of IL-17B genes of patients affected with this disease.

Amino Acid Sequence↗
PubMed1983

Chromatin structure differs between coding and upstream flanking sequences of the yeast 35S ribosomal genes.

Staphylococcal nuclease (EC 3.1.4.7) and DNase I (EC 3.1.4.5) digestion analysis of the nuclear chromatin structure of the yeast 35S rDNA gene shows the presence of typical and homogeneous nucleosome patterns across the coding sequence. These nucleosomal patterns change abruptly, around the site of transcription initiation and upstream in the 5'-flanking sequences, to a unique pattern with both nucleosomal and nonnucleosomal character. The mix arises, at least partly, from heterogeneity within the population of upstream regions; some regions are nucleosomal, but the majority are nonnucleosomal. The nonnucleosomal set of upstream regions appears to be nucleoprotein associated and, in fact, may be an altered nucleosome structure rather than totally restructured. The abruptness of the transition from nucleosome to other structure suggests restricted nucleosome locations in the region around the transcription initiation site of this gene.

Base Sequence↗
PubMed1985

Thyroid hormone regulates transcription of the gene for cytosolic phosphoenolpyruvate carboxykinase (GTP) in rat liver.

Using an in vitro assay with isolated rat nuclei, we have determined that thyroid hormone causes a 4-6-fold increase in the synthesis of mRNA coding for phosphoenolpyruvate carboxykinase. Proportional changes were seen in the steady-state cytosolic mRNA levels for phosphoenolpyruvate carboxykinase. Dibutyryladenosine cyclic 3',5'-monophosphate, which stimulates transcription of the phosphoenolpyruvate carboxykinase gene in normal rats, remained effective in hypo- or hyperthyroid animals. The effect of epinephrine on transcription of the gene for phosphoenolpyruvate carboxykinase appears to be modulated by thyroid hormone.

Animals↗
PubMed2003

Fourier phase and amplitude analysis for automated objective evaluation of myocardial contrast echocardiograms.

AIMS: Objective methods for evaluating myocardial contrast echocardiography (MCE) are not yet widely available. We applied a Fourier analysis to myocardial contrast echocardiograms to identify myocardial perfusion defects. METHODS: Harmonic power-Doppler contrast echocardiograms were performed in 21 patients undergoing Tl-201-SPECT imaging and in 13 controls. Images were transformed using Fourier analysis to obtain phase of the first harmonic sinusoidal curve displayed as color coded sequence of myocardial intensity changes. Means and standard deviations of regional phase angles were measured. The method was validated in an in vitro model. A contrast filled latex balloon was imaged at different gain settings mimicking defined time-intensity curves. An intraoperative porcine infarction model served to prove feasibility of Fourier transformation to analyze real-time pulse inversion contrast echocardiography. RESULTS: In patients, phase imaging and intensity analysis showed focal areas with marked phase shifts (106 +/- 90 degrees) and heterogeneous distribution of phase angles (SD 66 +/- 17 degrees), correctly identifying 13/14 perfusion defects. The in vitro validation yielded increasing phase angles with increasing beta-values. This method was successfully applied to real-time MCE, identifying all infarction areas during occlusion of the left anterior descending artery. CONCLUSION: Phase analysis can be used to display dynamics of myocardial opacification.

Aged↗
PubMedDate not supplied

Loss of spatial phase relationships in extrafoveal vision.

Objects in peripheral vision are not simply blurred but lack quality of form. Assuming that the visual system performs a (patchwise) Fourier analysis of the retinal image (for review see ref. 2), it has been suggested that this disadvantage of peripheral vision may be due to the inability to encode properly spatial phase relationships. This is of great interest for neurological research as certain visual pathologies imply alterations of perceived form. Previous attempts at measuring phase sensitivities failed to distinguish between the detection of phase-related changes in contrast and phase coding in the visual system. We separated these processing strategies by applying the iso-second-order texture paradigm of Julesz to the discrimination of compound gratings. Our results, reported here, show that the energy detection properties of both foveal and peripheral vision are comparable, however, independently of scale, peripheral vision ignores the relative position of image components.

Fovea Centralis↗
PubMed2002

Molecular evolution of FOXP2, a gene involved in speech and language.

Language is a uniquely human trait likely to have been a prerequisite for the development of human culture. The ability to develop articulate speech relies on capabilities, such as fine control of the larynx and mouth, that are absent in chimpanzees and other great apes. FOXP2 is the first gene relevant to the human ability to develop language. A point mutation in FOXP2 co-segregates with a disorder in a family in which half of the members have severe articulation difficulties accompanied by linguistic and grammatical impairment. This gene is disrupted by translocation in an unrelated individual who has a similar disorder. Thus, two functional copies of FOXP2 seem to be required for acquisition of normal spoken language. We sequenced the complementary DNAs that encode the FOXP2 protein in the chimpanzee, gorilla, orang-utan, rhesus macaque and mouse, and compared them with the human cDNA. We also investigated intraspecific variation of the human FOXP2 gene. Here we show that human FOXP2 contains changes in amino-acid coding and a pattern of nucleotide polymorphism, which strongly suggest that this gene has been the target of selection during recent human evolution.

Alleles↗
PubMed2002

Functional SNPs in the lymphotoxin-alpha gene that are associated with susceptibility to myocardial infarction.

By means of a large-scale, case-control association study using 92,788 gene-based single-nucleotide polymorphism (SNP) markers, we identified a candidate locus on chromosome 6p21 associated with susceptibility to myocardial infarction. Subsequent linkage-disequilibrium (LD) mapping and analyses of haplotype structure showed significant associations between myocardial infarction and a single 50 kb halpotype comprised of five SNPs in LTA (encoding lymphotoxin-alpha), NFKBIL1 (encoding nuclear factor of kappa light polypeptide gene enhancer in B cells, inhibitor-like 1) and BAT1 (encoding HLA-B associated transcript 1). Homozygosity with respect to each of the two SNPs in LTA was significantly associated with increased risk for myocardial infarction (odds ratio = 1.78, chi(2) = 21.6, P = 0.00000033; 1,133 affected individuals versus 1,006 controls). In vitro functional analyses indicated that one SNP in the coding region of LTA, which changed an amino-acid residue from threonine to asparagine (Thr26Asn), effected a twofold increase in induction of several cell-adhesion molecules, including VCAM1, in vascular smooth-muscle cells of human coronary artery. Moreover, the SNP, in intron 1 of LTA, enhanced the transcriptional level of LTA. These results indicate that variants in the LTA are risk factors for myocardial infraction and implicate LTA in the pathogenesis of the disorder.

Aged↗
PubMed1996

Molecular analysis of the presenilin 1 (S182) gene in "sporadic" cases of Alzheimer's disease: identification and characterisation of unusual splice variants.

Mutations of the presenilin 1 (PS-1) gene at the Alzheimer's disease (AD) FAD3 locus on chromosome 14q24.3 are responsible for the majority of familial early-onset AD. As genes responsible for familial forms of AD are obvious candidates for further investigation in "sporadic" disease, we performed a molecular analysis of PS-1 transcripts extracted from brain tissues of a series of histologically confirmed cases of "sporadic" AD (n=10) and also from histologically "normal" (non-Alzheimer) age-matched brain controls (n=5). No sequence changes in the PS-1 coding sequence were detected after analysis by reverse transcription-PCR. This suggests that the frequency of mutations in the PS-1 (S182) coding region in "sporadic" Alzheimer's disease in very low. However, we demonstrated that the PS-1 gene is highly variably spliced. One splice variant involves the 5' untranslated region of the PS-1 gene only and hence encodes for normal PS-1. Six further splice variants involve coding regions of the PS-1 gene and result in truncated proteins lacking specific transmembrane domains. Most of these variants do not coincide with recognized sites of introns in the PS-1 gene. One of these variants, resulting in the loss of transmembrane domain TM-VII, was found only in an AD patient.

Alternative Splicing↗
PubMed2001

Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias.

INTRODUCTION: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion channels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. METHODS AND RESULTS: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in approximately 11% of the Japanese population. This 1727G>A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S-KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT-KCNQ1 and G643S-KCNQ1 with KCNE1 resulted in approximately 30% reduction in the slow delayed rectifier K+ current I(Ks) without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. CONCLUSION: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild I(Ks) dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population.

Adult↗
PubMedDate not supplied

[Economic aspects of outpatient rehabilitation--methods and results of a study about economic efficiency of outpatient rehabilitation in Mecklenburg-Vorpommern].

Since the recent changes in the German social code the outpatient rehabilitation system gains importance. While more and more studies investigate the medical outcomes of outpatient rehabilitation, the economic effects have hardly been examined so far. This article first presents fundamental methods to use for economic evaluation of outpatient rehabilitation and subsequently outlines the findings of a project comparing the economic effects of outpatient and inpatient rehabilitation in Mecklenburg-Vorpommern. The study statistically covers the total population of applicants for orthopaedic-traumatologic rehabilitation who are suitable for outpatient rehabilitation. A randomized and controlled study, it investigates outcome parameters of the two variants of rehabilitation compared. If the results are approximately equal, the differences between amounts and periods of payments and costs for the pension insurance agency are analyzed. And in fact, the results obtained so far from the investigation confirm that, in suitable patients, outpatient rehabilitation can achieve approximately the same outcomes as inpatient rehabilitation - but at distinctly lower costs. Although in the short term (i. e., at the end of treatment) outcome levels are somewhat lower, better results found even one year later however indicate a more sustained effect.

Ambulatory Care↗
PubMed2006

A Dirichlet process model for detecting positive selection in protein-coding DNA sequences.

Most methods for detecting Darwinian natural selection at the molecular level rely on estimating the rates or numbers of nonsynonymous and synonymous changes in an alignment of protein-coding DNA sequences. In some of these methods, the nonsynonymous rate of substitution is allowed to vary across the sequence, permitting the identification of single amino acid positions that are under positive natural selection. However, it is unclear which probability distribution should be used to describe how the nonsynonymous rate of substitution varies across the sequence. One widely used solution is to model variation in the nonsynonymous rate across the sequence as a mixture of several discrete or continuous probability distributions. Unfortunately, there is little population genetics theory to inform us of the appropriate probability distribution for among-site variation in the nonsynonymous rate of substitution. Here, we describe an approach to modeling variation in the nonsynonymous rate of substitution by using a Dirichlet process mixture model. The Dirichlet process allows there to be a countably infinite number of nonsynonymous rate classes and is very flexible in accommodating different potential distributions for the nonsynonymous rate of substitution. We implemented the model in a fully Bayesian approach, with all parameters of the model considered as random variables.

Animals↗
PubMed1984

cis-acting mutations that affect rop protein control of plasmid copy number.

A number of pMB1 derivatives provide a trans-acting function that can suppress lethal runaway replication of a temperature-sensitive copy-number mutant of NTP1. Deletion analysis indicates that the region of the pMB1 genome that contains the rop gene is required for this suppression. Mutant derivatives of the temperature-sensitive copy-number mutant plasmid whose conditional lethal phenotype is not suppressed in trans by the region encoding the rop gene have been isolated. These rop-insensitive derivatives contain single nucleotide changes within the RNA I coding region.

Bacterial Proteins↗
PubMed1985

Loss of the normal N-ras allele in a mouse thymic lymphoma induced by a chemical carcinogen.

Young mice injected with the carcinogen N-nitroso-N-methylurea develop thymic lymphomas 2-4 months later. We previously have shown that these tumors frequently contain an activated N-ras gene that can transform rodent fibroblasts in vitro. We report here the intron/exon structure of such an activated N-ras gene and the sequence of its four coding exons. A single nucleotide change is responsible for the transforming alteration, a C----A transversion in the first base of codon 61. Through the use of synthetic oligonucleotides as hybridization probes, we show that this tumor lacks the normal allele of the N-ras gene. The implications of this finding for oncogene dominance are discussed.

Alleles↗
PubMed1990

Representational guidance of action production in observational learning: a causal analysis.

This experiment tested the hypothesis that the number of model presentations and verbal coding of modeled actions affect reproduction accuracy through their effect on cognitive representation. Subjects viewed a complex action pattern either two or eight times with or without verbal coding to highlight the dynamic structure of the component actions and their temporal sequencing. They then received, in order, a recognition test and a pictorial-arrangement test to assess the accuracy of their cognitive representations of the modeled actions. Subsequently, all subjects were tested for their ability to reproduce the action pattern from memory. Results showed that increased exposure to modeled actions enhanced the accuracy of both the cognitive representation and the behavioral reproduction. Verbal coding also increased cognitive and reproduction accuracy, but only when combined with multiple opportunities to observe the modeled actions. A causal analysis confirmed that the effects of multiple exposures and verbal coding were entirely mediated by changes produced in the accuracy of cognitive representation.

Journal Article↗
PubMed2005

Recent advancements in differential proteomics based on stable isotope coding.

Stable isotope coding continues to be a powerful approach in comparative proteomics. This review focuses on recent developments in stable isotope coding-based strategies targeted towards protein expression, protein interactions with other biomolecules, post-translational modifications and absolute quantification. The focus of the bulk of proteomics studies is still on protein expression. An important recent application of isotope coding has been in organelle proteomics. The review ends with the conclusion that isotope coding remains an integral part of quantitative proteomics. There is, however, a need to develop coding strategies which can differentiate changes in protein expression and post-translational modification, address issues of protein dynamic range and facilitate real-time detection of proteins which show a statistically significant change after stimulus.

Amino Acids↗
PubMed1997

Direct evidence for SIR2 modulation of chromatin structure in yeast rDNA.

The yeast SIR2 gene maintains inactive chromatin domains required for transcriptional repression at the silent mating-type loci and telomeres. We previously demonstrated that SIR2 also acts to repress mitotic and meiotic recombination between the tandem ribosomal RNA gene array (rDNA). Here we address whether rDNA chromatin structure is altered by loss of SIR2 function by in vitro and in vivo assays of sensitivity to micrococcal nuclease and dam methyltransferase, respectively, and present the first chromatin study that maps sites of SIR2 action within the rDNA locus. Control studies at the MAT alpha locus also revealed a previously undetected MNase-sensitive site at the a1-alpha 2 divergent promoter which is protected in sir2 mutant cells by the derepressed a1-alpha 2 regulator. In rDNA, SIR2 is required for a more closed chromatin structure in two regions: SRR1, the major SIR-Responsive Region in the non-transcribed spacer, and SRR2, in the 18S rRNA coding region. None of the changes in rDNA detected in sir2 mutants are due to the presence of the a1-alpha 2 repressor. Reduced recombination in the rDNA correlates with a small, reproducible transcriptional silencing position effect. Deletion and overexpression studies demonstrate that SIR2, but not SIR1, SIR3 or SIR4, is required for this rDNA position effect. Significantly, rDNA transcriptional silencing and rDNA chromatin accessibility respond to SIR2 dosage, indicating that SIR2 is a limiting component required for chromatin modeling in rDNA.

Chromatin↗
PubMed1990

The structure, distribution and evolution of the Ta1 retrotransposable element family of Arabidopsis thaliana.

The Ta1 elements are a low copy number, copia-like retrotransposable element family of Arabidopsis thaliana. Six Ta1 insertions comprise all of the Ta1 element copies found in three geographically diverse A. thaliana races. These six elements occupy three distinct target sites: Ta1-1 is located on chromosome 5 and is common to all three races (Col-0, Kas-1 and La-0). Ta1-2 is present in two races on chromosome 4 (Kas-1 and La-0), and Ta1-3, also located on chromosome 4, is present only in one race (La-0). The six Ta1 insertions share greater than 96% nucleotide identity, yet are likely to be incapable of further transposition due to deletions or nucleotide changes that alter either the coding capacity of the elements or conserved protein domains required for retrotransposition. Nucleotide sequence comparisons of these elements and the distribution of Ta1 among 12 additional A. thaliana geographical races suggest that Ta1-1 predated the global dispersal of A. thaliana. As the species spread throughout the world, two additional transposition events occurred which gave rise first to Ta1-2 and finally to Ta1-3.

Acyltransferases↗