Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “genetic code 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 613 records · Page 34Linked to original sources
PubMed2003

Identification of epistatic interaction involved in obesity using the KK/Ta mouse as a Type 2 diabetes model: is Zn-alpha2 glycoprotein-1 a candidate gene for obesity?

The KK/Ta strain serves as a suitable polygenic mouse model for the common form of type 2 diabetes associated with obesity in humans. Recently, we reported the susceptibility loci contributing to type 2 diabetes and related phenotypes in KK/Ta mice. In this study, we focused on expression in the kidneys and liver of KK/Ta and BALB/c mice using differential display (DD) PCR. Zn-alpha(2) glycoprotein-1 (Azgp1) mRNA levels were increased in the kidneys and liver in KK/Ta mice, and sequence analysis revealed a missense mutation. We analyzed the relationship between this polymorphism and various phenotypes in 208 KK/Ta x (BALB/c x KK/Ta) F1 backcross mice. Statistical analysis revealed that Azgp1 and D17Mit218 exhibit a suggestive linkage to body weight (8 weeks) (logarithm of odds 2.3 and 2.9, respectively). Moderate gene-gene interactions were observed at these loci. Adiponectin mRNA levels in 3T3-L1 cells transfected with the expression pcDNA 3.1 vector containing Azgp1 coding sequence of KK/Ta mice were significantly higher than those of BALB/c mice. These results suggest that Azgp1 is a possible candidate gene for regulation of body weight, elucidation of polygenic inheritance, and age-dependent changes in the genetic control of obesity.

Adiponectin↗
PubMed1993

The detection and characterization of multiple hemagglutinin-esterase (HE)-defective viruses in the mouse brain during subacute demyelination induced by mouse hepatitis virus.

It has previously been shown that passive immunization with antibodies specific for the hemagglutinin-esterase (HE) protein of mouse hepatitis virus (MHV) prevents acute lethal encephalitis, resulting in a subacute and chronic demyelination in mice infected with JHM(2), an isolate of the neurotropic JHM strain of MHV. To determine possible genetic changes occurring during infection, viruses were isolated from the brain of infected mice at various time points after infection and examined for the patterns of their structural proteins. The results showed that the sizes and expression levels of the viral spike, membrane, and nucleocapsid proteins were constant among 161 virus isolates throughout the infection. In contrast, most of the viruses isolated later in infection did not synthesize HE protein. This finding suggests that the HE gene expression is extremely variable and is preferentially lost during prolonged viral infections. In contrast, when viruses were passaged in tissue culture, no significant accumulation of HE protein-defective mutants was observed, suggesting that the accumulation of HE protein-defective mutants in infected animals was most likely the result of the positive selection for these mutants during the subacute and chronic infection. The genetic defects of HE gene in these mutants were characterized by cloning, sequencing, and in vitro translation of HE genes. Most of the mutations in the HE protein-defective mutants consisted of deletions of various lengths at different sites within the HE-coding region, resulting in the change of the reading frame and early termination. However, most of the truncated HE proteins were not detected in the infected cells. Since viruses from different mice exhibited different types of defects, the HE mutations probably occurred de novo in the brain. These results demonstrated the exceptionally rapid selection of HE-defective mutants during viral infection of mice and suggest that their selection may be related to the neuropathogenicity or persistence of MHV.

Animals↗
PubMed2003

A hospital-associated outbreak of Legionnaires' disease caused by Legionella pneumophila serogroup 1 is characterized by stable genetic fingerprinting but variable monoclonal antibody patterns.

An outbreak of 18 pneumonia cases caused by Legionella pneumophila serogroup 1 occurred at a Swedish university hospital 1996 to 1999. Eight clinical isolates obtained by culture from the respiratory tract were compared to 20 environmental isolates from the hospital and to 21 epidemiologically unrelated isolates in Sweden, mostly from patients, by using pulsed-field gel electrophoresis (PFGE), amplified fragment length polymorphism analysis (AFLP), and monoclonal antibody (MAb) typing. All patients and most environmental isolates from the outbreak hospital belonged to the same genotypic cluster in both PFGE and AFLP. This genotype was distinctly different from other strains, including a cluster from a second hospital in a different part of the country. The MAb subtype of the outbreak clone was Knoxville except for three isolates that were Oxford. A variation in the MAb reactivity pattern was also found in a second genotypic cluster. These changes in the MAb reactivity pattern were due to the absence or presence of the lag-1 gene coding for an O-acetyltransferase that is responsible for expression of the lipopolysaccharide epitope recognized by MAb 3/1 of the Dresden Panel. In all MAb 3/1-positive strains, the lag-1 gene was present on a genetic element that was bordered by a direct repeat that showed a high degree of sequence homology. Due to this homology, the lag-1 gene region seemed to be an unstable element in the chromosome. MAb patterns are thus a valuable adjunct to genotyping methods in defining subgroups inside a genotypic cluster of L. pneumophila sg 1.

Acetyltransferases↗
PubMed2000

Consensus temporal order of amino acids and evolution of the triplet code.

Forty different single-factor criteria and multi-factor hypotheses about chronological order of appearance of amino acids in the early evolution are summarized in consensus ranking. All available knowledge and thoughts about origin and evolution of the genetic code are thus combined in a single list where the amino acids are ranked chronologically. Due to consensus nature of the chronology it has several important properties not visible in individual rankings by any of the initial criteria. Nine amino acids of the Miller's imitation of primordial environment are all ranked as topmost (G, A, V, D, E, P, S, L, T). This result does not change even after several criteria related to Miller's data are excluded from calculations. The consensus order of appearance of the 20 amino acids on the evolutionary scene also reveals a unique and strikingly simple chronological organization of 64 codons, that could not be figured out from individual criteria: New codons appear in descending order of their thermostability, as complementary pairs, with the complements recruited sequentially from the codon repertoires of the earlier or simultaneously appearing amino acids. These three rules (Thermostability, Complementarity and Processivity) hold strictly as well as leading position of the earliest amino acids according to Miller. The consensus chronology of amino acids, G/A, V/D, P, S, E/L, T, R, N, K, Q, I, C, H, F, M, Y, W, and the derived temporal order for codons may serve, thus, as a justified working model of choice for further studies on the origin and evolution of the genetic code.

Amino Acids↗
PubMed2005

Murine candidate bleomycin induced pulmonary fibrosis susceptibility genes identified by gene expression and sequence analysis of linkage regions.

BACKGROUND: Pulmonary fibrosis is a complex disease for which the predisposing genetic variants remain unknown. In a prior study, susceptibility to bleomycin induced pulmonary fibrosis was mapped to loci Blmpf1 and Blmpf2 on chromosomes 17 and 11, respectively, in a C57BL/6J (B6, susceptible) and C3Hf/KAM (C3H, resistant) mouse cross. METHODS: Herein, the genetic basis of bleomycin induced pulmonary fibrosis was investigated in an approach combining gene expression and sequencing data with previously mapped linkage intervals. RESULTS: In this study, gene expression analysis with microarrays revealed 1892 genes or ESTs (expressed sequence tags) to be differentially expressed between bleomycin treated B6 and C3H mice and 67 of these genetic elements map to Blmpf1 or Blmpf2. This group included genes involved in an oxidative stress response, in apoptosis, and in immune regulation. A comparison of the B6 and C3H sequence, for Blmpf1 and Blmpf2, made using the NCBI database and available C3H sequence, revealed approximately 35% of the genes in these regions contain non-synonymous coding sequence changes. An assessment of genotype/phenotype correlation among other inbred strains revealed 36% of these B6/C3H sequence variations predict for the known bleomycin induced fibrosis susceptibility of the DBA (susceptible) and A/J (resistant) mouse strains. CONCLUSIONS: Combining genomics approaches of differential gene expression and sequence variation potentially identifies approximately 5% the linked genes as fibrosis susceptibility candidate genes in this mouse cross.

Animals↗
PubMed1979

The effect of trisomy 21 on the patterns of polypeptide synthesis in human fibroblasts.

In addition to direct gene dosage effects, the deleterious phenotypic consequences of aneuploidy may result from secondary regulatory effects on the production and degradation of gene products coded for by other chromosomes. In an initial test of the hypothesis that extensive secondary effects play an important role in the phenotypic consequences of aneuploidy, we have used two-dimensional gel electrophoresis with radioautography to look for such secondary effects among the polypeptides synthesized by human fibroblasts grown in vitro. The polypeptide patterns of fibroblast strains from four trisomy 21 subjects and one trisomy 21/normal mosaic were compared to those from five matched normal subjects. Of approximately 850 polypeptides visualized, only four show a pattern of variation which may be related to trisomy 21. Additional differences in polypeptide concentrations were found among the strains, attributable to genetic heterogeneity between donor individuals and differences in tissue of origin. These results indicate that, at least in fibroblasts in vitro, trisomy 21 does not cause major regulatory changes in the rates of production and degradation of a large number of polypeptides.

Adult↗
PubMed2001

A multiple-site-specific heteroduplex tracking assay as a tool for the study of viral population dynamics.

Rapidly evolving entities, such as viruses, can undergo complex genetic changes in the face of strong selective pressure. We have developed a modified heteroduplex tracking assay (HTA) capable of detecting the presence of single, specific mutations or sets of linked mutations. The initial application of this approach, termed multiple-site-specific (MSS) HTA, was directed toward the detection of mutations in the HIV-1 pro gene at positions 46, 48, 54, 82, 84, and 90, which are associated with resistance to multiple protease inhibitors. We demonstrate that MSS HTA is sensitive and largely specific to all targeted mutations. The assay allows the accurate and reproducible quantitation of viral subpopulations comprising 3% or more of the total population. Furthermore, we used MSS HTA in longitudinal studies of pro gene evolution in vitro and in vivo. In the examples shown here, populations turned over rapidly and more than one population was present frequently. To demonstrate the versatility of MSS HTA, we also constructed a probe sensitive to changes at positions 181 and 184 of the RT coding domain. Changes at these positions are involved in resistance to nevirapine and 2',3'-dideoxy-3'-thiacytidine (3TC), respectively. This assay easily detected the evolution of resistance to 3TC. MSS HTA provides a rapid and sensitive approach for detecting the presence of and quantifying complex mixtures of distinct genotypes, including genetically linked mutations, and, as one example, represents a useful tool for following the evolution of drug resistance during failure of HIV-1 antiviral therapy.

Antiviral Agents↗
PubMed2005

Differential excision patterns of the En-transposable element at the A2 locus in maize relate to the insertion site.

Defined mutant alleles with resident transposons display characteristic patterns of germinal and somatic reversion, and heritable changes in the timing and frequency of reversions, which have been termed "change of state" by McClintock, constantly arise. Several mechanisms were proposed to account for these changes. They may be ascribed to the structure and composition of the elements themselves (composition hypothesis) or to their location (position hypothesis). In the current study, insertion positions were determined for three autonomous En-controlled mutable alleles of the A2 locus in maize that show different somatic reversion patterns. A relationship was observed between En insertion positions in the single coding region of the intronless A2 gene and anthocyanin variegation patterns in the aleurone. An insertion in the 5' region of the coding sequence produced a very late somatic variegation pattern, whereas two early variegation patterns were caused by En insertions in the 3' region of the coding sequence.

Alleles↗
PubMed1988

Stop is not the end: physiological implications of translational readthrough.

The translational readthrough mechanism permits the occasional misreading of termination codons by normal charged tRNAs causing extended translation beyond the stop signal. In both prokaryotes and eukaryotes translational readthrough is involved in the regulation of gene expression, as for example in the synthesis of the enzyme reverse transcriptase of the Murine Leukemia Virus (MuLV) (Yoshinaka et al., 1985). Here we particularly deal with the sensitivity of the translational readthrough process to two parameters which are affected by changes in physiological conditions: (1) fluctuations in the concentration of readthrough tRNAs and (b) The affinity of the tRNAs to termination codons. We also discuss the possible role of translational readthrough during major changes in cell physiology.

Adaptation, Physiological↗
PubMed1984

Variation of levels of mRNA coding for antenna and reaction center polypeptides in Rhodopseudomonas capsulata in response to changes in oxygen concentration.

The effect of oxygen tension on the transcription of genes coding for the photosynthetic apparatus of Rhodopseudomonas capsulata was determined by the Southern hybridization technique. Restriction endonuclease digests of the R-prime plasmid pRPS404 and a subcloned fragment thereof served as DNA probes for genetically defined regions. The results showed that transcripts corresponding to the genes for certain pigment-binding polypeptides increase in amount by about 40-fold after a drop in oxygen tension. Transcripts hybridizing to genes involved in bacteriochlorophyll biosynthesis increase to a much lesser extent, and several genes involved in carotenoid biosynthesis are not affected by pO2.

Bacterial Proteins↗
PubMed2005

New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid protein (VP1) possibly associated with progressive multifocal leukoencephalopathy.

JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML) in patients with decreased immune competence. To elucidate genetic changes in JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones originating from the brains of three PML cases were established and sequenced. Although unique rearranged control regions occurred in all clones, a low level of nucleotide variation was also found in the coding region. In each case, a parental coding sequence was identified, from which variant coding sequences with nucleotide substitutions would have been generated. A comparison between the parental and variant coding sequences demonstrated that all 12 detected nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of these changes were located in the surface loops of the major capsid protein (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from the brain or cerebrospinal fluid of PML patients) were compared with their genotypic prototypes, generated as consensus sequences of representative archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino acid changes in the surface loops. In contrast, VP1 proteins from isolates from the urine of immunocompetent and immunosuppressed patients rarely underwent mutations in the VP1 loops. The present findings suggest that PML-type JCPyV frequently undergoes amino acid substitutions in the VP1 loops. These polymorphisms should serve as a new marker for the identification of JCPyV isolates associated with PML. The biological significance of these mutations, however, remains unclear.

Adult↗
PubMed2006

A novel nuclear-encoded mitochondrial poly(A) polymerase PAPD1 is a potential candidate gene for the extreme obesity related phenotypes in mammals.

People with obesity, especially extreme obesity, are at risk for many health problems. However, the responsible genes remain unknown in >95% of severe obesity cases. Our previous genome-wide scan of Wagyu x Limousin F2 cattle crosses with extreme phenotypes revealed a molecular marker significantly associated with intramuscular fat deposition. Characterization of this marker showed that it is orthologous to the human gene KIAA1462 located on HSA10p11.23, where a major quantitative trait locus for morbid obesity has been reported. The newly identified mitochondrial poly(A) polymerase associated domain containing 1 (PAPD1) gene, which is located near this marker, is particularly interesting because the polymerase is required for the polyadenylation and stabilization of mammalian mitochondrial mRNAs. In the present study, both cDNA and genomic DNA sequences were annotated for the bovine PAPD1 gene and ten genetic markers were detected in the promoter and exon 1 region. Among seven markers assayed on approximately 250 Wagyu x Limousin F2 animals, two single nucleotide polymorphisms (SNPs) in the promoter region were significantly associated with intramuscular fat (P<0.05). However, there was a significant interaction (P<0.05) between a third SNP, which causes an amino acid change in coding exon 1, and each of these two promoter SNPs on intramuscular fat deposition. In particular, the differences between double heterozygous animals at two polymorphic sites and the slim genotype animals exceeded 2.3 standard deviations for the trait in both cases. Our study provides evidence for a new mechanism--the involvement of compound heterosis in extreme obesity, which warrants further examination.

Adipose Tissue↗
PubMed1990

Efficient transformation of chicken embryo fibroblasts by c-Jun requires structural modification in coding and noncoding sequences.

To assess the transforming capability of the c-Jun protein, we introduced the chicken c-jun proto-oncogene into a replication competent avian retroviral expression vector (RCAS). Viral Jun efficiently transformed chicken embryo fibroblasts (CEFs) when expressed from this vector. Overexpression of c-Jun leads to transformation of CEFs with an efficiency that is 15- to 25-fold less than that seen for v-Jun, suggesting that v-Jun contains structural features that increase its oncogenic potential relative to c-Jun. There are four structural differences between v-Jun and c-Jun. To determine the relative contribution that each of these structural differences between v-Jun and c-Jun has on oncogenic activity, several deletion and substitution mutants were constructed. Each of these mutants was expressed in CEF and assayed for transformation by focus formation. Analysis of the results reveals that deletion of a region of 27 amino acids near the amino terminus of c-Jun and deletion of 3'-untranslated sequences are critical in activating the full oncogenic potential of Jun.

Amino Acid Sequence↗
PubMed2006

CHST6 mutations in North American subjects with macular corneal dystrophy: a comprehensive molecular genetic review.

PURPOSE: To evaluate mutations in the carbohydrate sulfotransferase-6 (CHST6) gene in American subjects with macular corneal dystrophy (MCD). METHODS: We analyzed CHST6 in 57 patients from 31 families with MCD from the United States, 57 carriers (parents or children), and 27 unaffected blood relatives of affected subjects. We compared the observed nucleotide sequences with those found by numerous investigators in other populations with MCD and in controls. RESULTS: In 24 families, the corneal disorder could be explained by mutations in the coding region of CHST6 or in the region upstream of this gene in both the maternal and paternal chromosome. In most instances of MCD a homozygous or heterozygous missense mutation in exon 3 of CHST6 was found. Six cases resulted from a deletion upstream of CHST6. CONCLUSIONS: Nucleotide changes within the coding region of CHST6 are predicted to alter the encoded protein significantly within evolutionary conserved parts of the encoded sulfotransferase. Our findings support the hypothesis that CHST6 mutations are cardinal to the pathogenesis of MCD. Moreover, the observation that some cases of MCD cannot be explained by mutations in CHST6 suggests that MCD may result from other subtle changes in CHST6 or from genetic heterogeneity.

5' Untranslated Regions↗
PubMed2003

Evolution of phage with chemically ambiguous proteomes.

BACKGROUND: The widespread introduction of amino acid substitutions into organismal proteomes has occurred during natural evolution, but has been difficult to achieve by directed evolution. The adaptation of the translation apparatus represents one barrier, but the multiple mutations that may be required throughout a proteome in order to accommodate an alternative amino acid or analogue is an even more daunting problem. The evolution of a small bacteriophage proteome to accommodate an unnatural amino acid analogue can provide insights into the number and type of substitutions that individual proteins will require to retain functionality. RESULTS: The bacteriophage Qbeta initially grows poorly in the presence of the amino acid analogue 6-fluorotryptophan. After 25 serial passages, the fitness of the phage on the analogue was substantially increased; there was no loss of fitness when the evolved phage were passaged in the presence of tryptophan. Seven mutations were fixed throughout the phage in two independent lines of descent. None of the mutations changed a tryptophan residue. CONCLUSIONS: A relatively small number of mutations allowed an unnatural amino acid to be functionally incorporated into a highly interdependent set of proteins. These results support the 'ambiguous intermediate' hypothesis for the emergence of divergent genetic codes, in which the adoption of a new genetic code is preceded by the evolution of proteins that can simultaneously accommodate more than one amino acid at a given codon. It may now be possible to direct the evolution of organisms with novel genetic codes using methods that promote ambiguous intermediates.

Allolevivirus↗
PubMed1992

[Classical fowl plague and milder influenza infections in birds and mammals].

Wild waterfowl are currently considered the largest reservoir of the various haemagglutinin (H) and neuraminidase (N) subtypes of influenza virus. Until now thirteen different H-types and nine different N-types have been detected in these populations. In the first instance, virus transmission from fowl to other animal species and to man is not causing disease problems. However, small changes at the molecular level of a given HN-subtype recently caused a dramatic increase in virulence for chickens. Genes fragments coding for haemagglutinin or neuraminidase can be exchanged between viruses which propagate in the same individual. This phenomenon-'genetic reassortment'-is of major epidemiological significance when it occurs in pigs. New influenza epidemics in the human population consistently originate in areas where waterfowl, pigs and human beings live close together. At the moment, the virological and serological diagnosis of influenza A infections is based ELISAs for antigen and antibody detection. Both ELISAs employ a monoclonal antibody directed against a conserved antigenic determinant of the influenza A nucleoprotein. The use of these tests can simplify the diagnosis of and screening for influenza A infections, particularly in those species which harbour several H- and N-subtypes.

Animals↗