Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Codon”

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 145 records · Page 8Linked to original sources
PubMed2002

Coexistence of a novel beta-globin gene deletion (codons 81-87) with the codon 30 (G-->C) mutation in an Indian patient with beta0-thalassemia.

We identified and characterized a novel beta0-thalassemia mutation due to the deletion of 22 bases from codons 81 through 87, found in a compound heterozygous state with codon 30 (G-->C) in a patient originating from West Bengal State, India. The deletion causes a shift in the reading frame of the coding sequence and creates a stop codon at position 81. Direct and inverted repeat sequences present in the deleted region might be involved in the origin of this mutation. The patient had moderate anemia and did not require blood transfusions (thalassemia intermedia).

Base Sequence↗
PubMed1996

Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Sträussler-Scheinker disease (PrP-P102L mutation).

We present a new, large, Italian family affected by Gerstmann-Sträussler-Scheinker syndrome (GSS) associated with the Pro to Leu point mutation at codon 102 of the prion protein gene (PRNP). The affected members of this family show a remarkable phenotypic variability of the disease: three of them had a clinical picture characterized by dementia and a brief illness duration (less than 1 year), while the other five members presented an ataxic, slowly evolving syndrome (a clinical duration of 3 to 4 years) with no evidence of cognitive impairment. Despite these remarkable clinical differences among affected members, we found no correlation between the clinical presentation and the codon 129 or codon 219 genotypes. These data suggest that factors as yet unidentified may influence the clinical expression of the disease.

Aged↗
PubMed2002

A novel beta0-thalassemia mutation at codon 55 (-A) and a rare 17 bp deletion at codons 126-131 in the Indian population.

A new mutation at codon 55 (-A) and a rare mutation, a 17 bp deletion at codons 126-131, that gives rise to beta0-thalassemia, were found in the Indian population by means of direct sequencing of two polymerase chain reaction products generated from a 2.3 kb DNA fragment containing the whole beta-globin gene. Each polymerase chain reaction product was sequenced on both strands in a mutation-loading format, showing all nucleotide substitutions or deletions/insertions, including mutations and polymorphisms, in the product. The entire protocol requires four sequencing reactions/gel loadings after two successive polymerase chain reactions, which simplifies the mutation search process and reduces the reading error rate.

Adult↗
PubMed1994

Selenocysteine insertion or termination: factors affecting UGA codon fate and complementary anticodon:codon mutations.

Translation of UGA as selenocysteine instead of termination occurs in numerous proteins, and the process of recording UGA requires specific signals in the corresponding mRNAs. In eukaryotes, stem-loops in the 3' untranslated region of the mRNAs confer this function. Despite the presence of these signals, selenocysteine incorporation is inefficient. To investigate the reason for this, we examined the effects of the amount of deiodinase cDNA on UGA readthrough in transfected cells, quantitating the full-length and UGA terminated products by Western blotting. The gene for the selenocysteine-specific tRNA was also cotransfected to determine if it was limiting. We find that the concentrations of both the selenoprotein DNA and the tRNA affect the ratio of selenocysteine incorporation to termination. Selenium depletion was also found to decrease readthrough. The fact that the truncated peptide is synthesized intracellularly demonstrates unequivocally that UGA can serve as both a stop and a selenocysteine codon in a single mRNA. Mutation of UGA to UAA (stop) or UUA (leucine) in the deiodinase mRNA abolishes deiodinase activity; but activity is partially restored when selenocysteine tRNAs containing complementary mutations are contransfected. Thus, UGA is not essential for selenocysteine incorporation in mammalian cells, provided that codon:anticodon complementarity is maintained.

Anticodon↗
PubMed1992

Ocular findings associated with rhodopsin gene codon 17 and codon 182 transition mutations in dominant retinitis pigmentosa.

Six members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-thymine transition mutation in the second nucleotide of codon 17 in the rhodopsin gene that resulted in a threonine to methionine change. Three members from another family with autosomal dominant retinitis pigmentosa showed a guanine-to-adenine transition mutation in the first nucleotide of codon 182 in the rhodopsin gene that resulted in a glycine to serine change. Each of these two mutations presented with a similar phenotype because both showed a regional predilection for pigmentary changes to occur in the inferior part of the retina as well as field impairment predominantly in the superior hemisphere. Electroretinographic amplitudes were more substantial than usually encountered in other forms of retinitis pigmentosa, a finding consistent with the better visual prognosis in patients with either of these two mutations. This article documents the association of two similar phenotypes of autosomal dominant retinitis pigmentosa with specific gene defects at a molecular level.

Adolescent↗
PubMed1990

Translation of hepatitis B virus DNA polymerase from the internal AUG codon, not from the upstream AUG codon for the core protein.

Hepatitis B virus DNA replicates via its own polymerase that also acts as reverse transcriptase (Summers and Mason, 1982). This enzyme is encoded by a 3.5 Kb mRNA transcript covering the whole genome. Since the same transcript also codes for the core protein, and since the core open reading frame (ORF) is located upstream of the pol ORF, it has been suggested that the polymerase is first produced as a core-pol fusion protein that subsequently undergoes cleavage. This is already known to be the case with retrovirus reverse transcriptase, for which a gag-pol fusion protein is made first and the latter protein is liberated by proteolytic cleavage. We investigated this problem using mutants that were modified at the translation initiation codon for the core and precore ORF. Our findings suggested that polymerase translation occurred from the internal AUG codon independently of core protein synthesis, and that obligatory production of the core-pol fusion protein is accordingly unlikely.

Base Sequence↗
PubMed1987

Alteration of the ATG start codon of the A protein of bacteriophage phi X174 into an ATT codon yields a viable phage indicating that A protein is not essential for phi X174 reproduction.

Bacteriophage phi X174 gene A encodes two proteins: the gene A protein and the smaller A protein, which is synthesized from a translational start signal within the A gene in the same reading frame as the gene A protein. The gene A protein is involved in initiation, elongation and termination of rolling circle DNA replication. The role of the A protein in the life cycle of phi X174, however, is unknown. Using oligonucleotide-directed mutagenesis a viable phi X174 mutant was constructed in which the ATG start codon of the A protein was changed into an ATT codon. This mutant, phi X-4499T, does not synthesize A protein. The burst size of phi X-4499T amounted to 50% of that of wild type phi X174. This indicates that A protein, although advantageous for phage reproduction, is not essential during the life cycle of bacteriophage phi X174.

Bacteriophage phi X 174↗
PubMed1988

Phenotypic and reversion analysis of a Salmonella typhimurium constructed to have an arginine codon at the hisG46 missense codon.

Of the 6 single-base mutations that would be predicted to change the missense mutation hisG46 away from a proline codon in the Salmonella/microsome mutagen selection assay for histidine-independent revertants, only 5 have been observed. We have used site-specific mutagenesis to make the unobserved mutant [CCC (proline)----CGC (arginine)] codon in the Salmonella genome. Experiments with this arginine mutant demonstrate that, like bacteria containing the hisG46 mutation, bacteria with the arginine missense mutation are histidine auxotrophs which are capable of reversion to histidine independence. However, unlike the ATP phosphoribosyltransferase coded by the hisG46 his G gene (with a proline), the arginine mutant enzyme is partially active. This is indicated by a histidine-independent phenotype when the arginine hisG gene is present in multiple copies.

ATP Phosphoribosyltransferase↗
PubMed2005

Plant codon optimized cry genes of Bacillus thuringiensis can be expressed as soluble proteins in Escherichia coli BL21 Codon Plus strain as NusA-Cry protein fusions.

For optimal expression of delta-endotoxins from Bacillus thuringiensis in plants, preferential changes in the codon sequences, and reduction in overall AT content in the nucleotide sequence of the genes is important. Reports suggest that sequences with such modifications cannot be overexpressed in bacteria. We report here that the modified genes can be overexpressed in a strain of Escherichia coli carrying extra tRNA genes for some of the codons occurring at high frequency in plant genes and less preferred in E. coli. We also demonstrate that proteins when expressed as fusion products with NusA protein, are obtained as soluble fraction rather than in inclusion bodies. This allows easy and accurate LC50 analysis on insect pests.

Animals↗
PubMed1992

A heterozygous mutation (the codon for Ser447----a stop codon) in lipoprotein lipase contributes to a defect in lipid interface recognition in a case with type I hyperlipidemia.

Previously, we reported a case with type I hyperlipidemia due to a lipid interface recognition deficiency in lipoprotein lipase (LPL) (1). The LPL from postheparin plasma of this patient did not hydrolyze TritonX-100-triolein or very low density lipoprotein-triolein but did hydrolyze tributyrin and LysoPC-triolein substrates. Sequence analysis of the probands DNA revealed a heterozygous nucleotide change: a C----G transversion at position of 1595, resulting in changing the codon for Ser447 to a stop codon. Expression studies of this mutant LPLcDNA in Cos-1 cells produced and secreted considerable amounts of LPL mass in the culture media. The mutated LPL hydrolyzed much less TritonX-100-triolein than wild type LPL, whereas hydrolysis of tributyrin and LysoPC--triolein was the same with both the mutant and wild type LPL. These results suggest that this mutation might be responsible for the property of the LPL with a defect in lipid interface recognition in the type I patient we reported.

Adipose Tissue↗
PubMed2003

P53 (codon 72) and P21 (codon 31) polymorphisms alter in vivo mRNA expression of p21.

p21 (Waf1/Cip1) is a downstream target of p53. We evaluated the association between p21 polymorphism (codon 31), p53 polymorphism (codon 72) and their corresponding in vivo mRNA expression. In this study, p21 and p53 genetic polymorphisms (using standard PCR-RFLP techniques) and p21 and p53 gene expressions (using a radiolabelled ribonuclease protection assay (RPA) technique) were evaluated in the peripheral leukocytes of 84 individuals (63 with lung cancer). Log-transformed values of mRNA expression by RPA, which approximated a normal distribution, were analyzed. p53 genotypes did not correlate with p53 mRNA log-expression (P>0.05 for all comparisons), but the Pro allele variants of p53 were associated with a significant decrease in mRNA log-expression of its downstream target, p21. The variant Arg allele of p21 was also associated with a significant decrease in p21 mRNA log-expression. When individuals with at least one variant allele of both p53 and p21 (double-variants) were compared with all other genotype groups, these double-variants had significantly lower log-expression of p21 (P<0.005 by both t-tests (crude) and linear regression analyses (adjusted)). This is translated into an approximate 48% reduction in the geometric mean of the mRNA expression of the double-variants, when compared with all other groups. Results were consistent in both patients with lung cancer (n=63) and in normal controls (n=21). In conclusion, the presence of a p53 Pro allele and/or p21 Arg allele is associated with lower downstream target gene expression of p21.

Aged↗
PubMed2001

Analysis of codon:anticodon interactions within the ribosome provides new insights into codon reading and the genetic code structure.

Although the decoding rules have been largely elucidated, the physical-chemical reasons for the "correctness" of codon:anticodon duplexes have never been clear. In this work, on the basis of the available data, we propose that the correct codon:anticodon duplexes are those whose formation and interaction with the ribosomal decoding center are not accompanied by uncompensated losses of hydrogen and ionic bonds. Other factors such as proofreading, base-base stacking and aminoacyl-tRNA concentration contribute to the efficiency and accuracy of aminoacyl-tRNA selection, and certainly these factors are important; but we suggest that analyses of hydrogen and ionic bonding alone provides a robust first-order approximation of decoding accuracy. Thus our model can simplify predictions about decoding accuracy and error. The model can be refined with data, but is already powerful enough to explain all of the available data on decoding accuracy. Here we predict which duplexes should be considered correct, which duplexes are responsible for virtually all misreading, and we suggest an evolutionary scheme that gave rise to the mixed boxes of the genetic code.

Anticodon↗
PubMed2005

Two French Caucasian families with dominant thalassemia-like phenotypes due to hyper unstable hemoglobin variants: Hb Sainte Seve [codon 118 (-T)] and codon 127 [CAG-->TAG (Gln-->stop]).

We report two French Caucasian families suffering from dominant thalassemia-like phenotypes due to hyper unstable hemoglobin (Hb) variants. In both cases, molecular analysis revealed a defect localized in the third exon of the beta-globin gene, resulting in dramatic changes of the Hb structure. The first one is a new variant, Hb Sainte Seve, that is associated with a frameshift mutation at codon 118 (-T). In the second family, the disease resulted from a truncated protein due to a stop mutation at codon 127 [CAG-->TAG (Gln-->Stop)]. These two observations are additional evidences of the important role played by helix H in Hb stability: its partial absence, or a large structural modification, seems to be the major reason for the hyper instability of such molecules.

Adult↗
PubMed2002

Conservation of translation initiation sites based on dinucleotide frequency and codon usage in Escherichia coli K-12 (W3110): non-random distribution of A/T-rich sequences immediately upstream of the translation initiation codon.

Dinucleotide frequencies are useful for characterizing consensus elements as a minimum unit of nucleotide sequence because the neighborhood relations of nucleotide sequences are reflected in dinucleotides. Using a consensus score based on dinucleotide frequencies and intra-species codon usage heterogeneity, denoted by the Z1 parameter, we report the relationship between nucleotide conservation at the translation initiation sites of genes in the Escherichia coli K-12 genome (W3110) and codon usage in its downstream genes. Significant positive correlations were obtained in three regions centered at -13, -4, and +7, which correspond to the Shine-Dalgarno element, the A + T element immediately upstream of the translation initiation site, and the downstream box, respectively.

Base Sequence↗
PubMed2000

Relative replication fitness of a high-level 3'-azido-3'-deoxythymidine-resistant variant of human immunodeficiency virus type 1 possessing an amino acid deletion at codon 67 and a novel substitution (Thr-->Gly) at codon 69.

The combination of an amino acid deletion at codon 67 (delta 67) and Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) is associated with high-level resistance to multiple RT inhibitors. To determine the relative contributions of the delta 67 and T69G mutations on viral fitness, we performed a series of studies of HIV replication using recombinant variants. A high-level 3'-azido-3'-deoxythymidine (AZT)-resistant variant containing delta 67 plus T69G/K70R/L74I/K103N/T215F/K219Q in RT replicated as efficiently as wild-type virus (Wt). In contrast, the construct without delta 67 exhibited impaired replication (23% of growth of Wt). A competitive fitness study failed to reveal any differences in replication rates between the delta 67+T69G/K70R/L74I/K103N/T215F/+ ++K219Q mutant and Wt. Evaluation of proviral DNA sequences over a 3-year period in a patient harboring the multiresistant HIV revealed that the T69G mutation emerged in the context of a D67N/K70R/T215F/K219Q mutant backbone prior to appearance of the delta 67 deletion. To assess the impact of this stepwise accumulation of mutations on viral replication, a series of recombinant variants was constructed and analyzed for replication competence. The T69G mutation was found to confer 2',3'-dideoxyinosine resistance at the expense of fitness. Subsequently, the development of the delta 67 deletion led to a virus with improved replication and high-level AZT resistance.

Anti-HIV Agents↗
PubMed2001

Amino acid deletion at codon 67 and Thr-to-Gly change at codon 69 of human immunodeficiency virus type 1 reverse transcriptase confer novel drug resistance profiles.

The potential roles of an amino acid deletion at codon 67 (Delta67) and a Thr-to-Gly change at codon 69 (T69G) in the reverse transcriptase of human immunodeficiency virus (HIV) type 1 in drug sensitivity and relative replication fitness were studied. Our results suggest that the Delta67 and T69G changes can be categorized as mutations associated with multidrug resistance. The combination of both mutations with an L74I change (Delta67+T69G/L74I) leads to a novel 3'-azido-3'-deoxythymidine resistance motif and compensates for impaired HIV replication.

Amino Acid Motifs↗
PubMed1995

Gerstmann-Sträussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients.

We present two patients with Gerstmann-Sträussler-Scheinker disease (GSS), one from a previously undescribed kindred and one from the Canadian branch of a previously reported British kindred. In both patients, GSS is caused by a substitution of thymine for cytosine at codon 102 of the prion protein gene (PRNP). In each patient, we confirmed the clinical diagnosis by neuropathologic examination. The mutation, causing a substitution of leucine for proline at residue 102 (P102L) of the prion protein, has been previously reported in at least 30 other families. In the patients described here, the mutation was in coupling with methionine at PRNP codon 129.

Adult↗