SEARCH · PubMed Health

Results for “Stop codon”

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 37 records · Page 2Linked to original sources

PubMed1990

Acute intermittent porphyria caused by a C----T mutation that produces a stop codon in the porphobilinogen deaminase gene.

A mutation of the porphobilinogen (PBG) deaminase gene that produces the cross-reacting immunological material (CRIM)-negative type of acute intermittent porphyria (AIP) has been identified in one of 43 unrelated patients with this form of the disorder. The mutation is a C----T transition that abolishes a PstI recognition site in exon 9 of the gene and converts a codon for glutamine to a stop codon.

Codon↗

PubMed1991

Stop codon in the procollagen II gene (COL2A1) in a family with the Stickler syndrome (arthro-ophthalmopathy).

Linkage analysis with restriction fragment length polymorphisms for the gene for type II procollagen (COL2A1) was carried out in a family with the Stickler syndrome, or arthro-ophthalmopathy, an autosomal dominant disorder that affects the eyes, ears, joints, and skeleton. The analysis demonstrated linkage of the disease and COL2A1 with a logarithm-of-odds score of 1.51 at zero recombination. A newly developed procedure for preparing cosmid clones was employed to isolate the allele for type II procollagen that was linked to the disease. Analysis of over 7000 nucleotides of the gene revealed a single base mutation that altered a CG dinucleotide and converted the codon CGA for arginine at amino acid position alpha 1-732 to TGA, a stop codon. From previous work on procollagen biosynthesis, it is apparent that the truncated polypeptide synthesized from an allele with a stop codon at alpha 1-732 cannot participate in the assembly of type II procollagen, and therefore that the mutation would decrease synthesis of type II procollagen. It was not apparent, however, why the mutation produced marked changes in the eye, which contains only small amounts of type II collagen, but relatively mild effects on the many cartilaginous structures of the body that are rich in the same protein.

Base Sequence↗

PubMed1991

Mutations in 16S rRNA that affect UGA (stop codon)-directed translation termination.

Site-directed mutagenesis was performed on a sequence motif within the 3' major domain of Escherichia coli 16S rRNA shown previously to be important for peptide chain termination. Analysis of stop codon suppression by the various mutants showed an exclusive response to UGA stop signals, which was correlated directly with the continuity of one or the other of two tandem complementary UCA sequences (bases 1199-1204). Since no other structural features of the mutated ribosomes were hampered and the translation initiation and elongation events functioned properly, we propose that a direct interaction occurs between the UGA stop codon on the mRNA and the 16S rRNA UCA motif as one of the initial events of UGA-dependent peptide chain termination. These results provide evidence that base pairing between rRNA and mRNA plays a direct role in termination, as it has already been shown to do for initiation and elongation.

Base Sequence↗

PubMed1989

Characterization of EcoRI mutation in fucosidosis patients: a stop codon in the open reading frame.

Recently, a subset of fucosidosis patients was identified in which the single EcoRI site in the open reading frame of the human cDNA encoding alpha-L-fucosidase was obliterated. We have employed the polymerase chain reaction technique to amplify alpha-L-fucosidase DNA from the five patients known to carry the EcoRI abnormality as well as four patients and two additional fucosidosis patients who do not carry the EcoRI abnormality. Sequence analysis of the amplified DNA has determined that the EcoRI site was destroyed by a C-T transition in the last position of the EcoRI site. This single base change results in the generation of a stop codon 120 base pairs upstream of the normal stop codon. In addition, we have determined that EcoRI cleavage of amplified DNA may be a useful diagnostic tool in the diagnosis of heterozygotes and in prenatal diagnosis of fetuses at risk for this disease.

Amino Acid Sequence↗

PubMed1991

Molecular basis for hereditary antithrombin III quantitative deficiencies: a stop codon in exon IIIa and a frameshift in exon VI.

Antithrombin III (AT III) is an inhibitor of serine protease (serpin) comprising 432 amino acids. Quantitative AT III deficiencies are associated with a high risk of thrombotic disease. Although this risk is smaller in patients with qualitative AT III deficiencies, the molecular defects characterizing the latter have been the subject of many studies. However, in quantitative AT III deficiencies, only three mutations have been described: Pro 407 to Leu and A1a404 to Thr (both located in the C-terminal part of the AT III molecule) and also a frameshift in exon IIIa. Using the asymmetric polymerase chain reaction (PCR) and genomic DNA analysis by direct sequencing, we detected two mutations in three unrelated families: (i) a C----T transition in exon IIIa in two families, leading to the replacement of the codon corresponding to Arg 129 by a stop codon, and (ii) in the third family, insertion of an adenine in the codon corresponding to Phe 408, a highly conserved serpin amino acid. This insertion altered the reading frame and led to the appearance of a premature stop signal. Patients of all three families were heterozygous for their abnormality. These results show that asymmetric PCR and genomic DNA analysis by direct sequencing permit fast identification of the molecular basis of quantitative AT III deficiencies. It is concluded that in many cases the absence of AT III gene product probably results from point mutation, as previously observed for another serpin, alpha-1-antitrypsin.

Adolescent↗

PubMed1990

Frameshift mutation in exon 3 of the lipoprotein lipase gene causes a premature stop codon and lipoprotein lipase deficiency.

Several mutations in the human lipoprotein lipase (LPL) gene have been shown to underlie LPL deficiency. These mutations occur in patients who are mainly of European descent, and comprise a single base transition causing a premature stop codon, four separate amino acid substitutions and two large gene rearrangements. Together they account for approximately 40% of the LPL alleles in a cohort of 50 patients whose DNA has been examined in this laboratory. We now report on a new mutation in exon 3 of the LPL gene from a South African subject of South-east Asian extraction. This mutation comprises a six base-pair insertion at the site of a single base deletion. The net insertion of five base-pairs at amino acid positions 102 to 103 causes a shift in the reading frame, generating 44 amino acid residues of random sequence and a premature stop codon within exon 4. This mutation is predicted to result in the synthesis of a markedly truncated protein and is the cause of the enzyme deficiency in our patient.

Adult↗

PubMed1992

A mutation generating a stop codon in the alpha-L-fucosidase gene of a fucosidosis patient.

Fucosidosis is an autosomal recessive, lysosomal storage disease featured by deficient activity of alpha-L-fucosidase. Lymphoid cell lines from a fucosidosis patient (JT) and a healthy individual (control) contained alpha-L-fucosidase mRNA of the same size, 2.3 Kb, as determined by Northern blot analysis. cDNA was prepared from alpha-L-fucosidase mRNA of JT and control cells and each cDNA was amplified by the polymerase chain reaction. Direct DNA sequencing of the amplified products revealed a single mutation in JT, a G1141-->T transition. This changed the codon (GAA) for Glu-375 to a stop codon (UAA). Amplification and sequencing of the area containing the G1141-->T transition in genomic DNA of JT and control cells demonstrated that the mutation was homozygous in JT. Analysis of cDNA and genomic DNA derived from lymphoid cells of mother JT revealed her to be heterozygous (G and T) at position 1141. The G1141-->T mutation is probably responsible for disease in JT.

B-Lymphocytes↗

PubMed1988

Genetic code development by stop codon takeover.

A novel theoretical consideration of the origin and evolution of the genetic code is presented. Code development is viewed from the perspective of simultaneously evolving codons, anticodons and amino acids. Early code structure was determined primarily by thermodynamic stability considerations, requiring simplicity in primordial codes. More advanced coding stages could arise as biological systems became more complex and precise in their replication. To be consistent with these ideas, a model is described in which codons become permanently associated with amino acids only when a codon-anticodon pairing is strong enough to permit rapid translation. Hence all codons are essentially chain-termination or "stop" codons until tRNA adaptors evolve having the ability to bind tightly to them. This view, which draws support from several lines of evidence, differs from the prevalent thinking on code evolution which holds that codons specifying newer amino acids were derived from codons encoding older amino acids.

Amino Acids↗

PubMed1990

An abnormal splice donor site in one allele of the thyroid peroxidase gene in FRTL5 rat thyroid cells introduces a premature stop codon: association with the absence of functional enzymatic activity.

Low stringency screening of an FRTL5 cDNA library with a human thyroid peroxidase (TPO) cDNA probe yielded two different types of TPO cDNA clones. One type contained the full-length structural gene, but there was an A at the first nucleotide of an intronic splice donor site that leads to alternate splicing, with the retention of part of an intron. This 54-basepair retained intron fragment contains a premature inframe stop codon that would truncate the protein at its carboxyl-terminus by 71% with the loss of enzymatic activity. The second type of TPO cDNA does not contain the retained intron fragment and premature stop codon, but it is not full-length and lacks 580-680 basepairs at its 5' end. However, Northern blot analysis reveals only full-length copies (3.2 kilobases) of TPO mRNA in FRTL5 cells, and this 5' truncation is, therefore, an artifact of library construction. The relative proportions of the two types of TPO mRNA in FRTL5 cells was determined by the polymerase chain reaction, using as template single stranded cDNA generated by reverse transcription of FRTL5 mRNA. Slightly more than half of the TPO mRNA in the FRTL5 cells represented the form with the abnormal splice donor site. The relative proportions of the two TPO mRNA forms was not influenced by TSH stimulation of the FRTL5 cells, and the proportion remained unaltered even after the FRTL5 cells were subcloned by limiting dilution. At the genomic level, we used allele-specific oligonucleotides for the mutant and normal forms of TPO, and found FRTL5 cells to have both normal and abnormal TPO alleles.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗

PubMed1988

Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a stop codon in the N-terminal region of 17 alpha-hydroxylase cytochrome P-450.

Steroid 17 alpha-hydroxylase (cytochrome P-450(17)alpha) mediates both 17 alpha-hydroxylase and 17,20-lyase activities. A relatively rare disease, 17 alpha-hydroxylase deficiency is characterized by defects in either or both of these activities. The molecular basis for variability of the defect is not well understood. We have determined the exonic sequence of the mutant P-450(17)alpha gene from one Japanese patient with combined 17 alpha-hydroxylase/17,20-lyase deficiencies. A stop codon (TGA) due to a single point mutation was found at the position of amino acid 17 in exon 1 of the P-450(17)alpha gene. The presence of a stop codon in the N-terminal region of this gene leads to the absence of a functional P-450(17)alpha protein in adrenal cortex and ovary, and consequently hypertension, primary amenorrhea and osteoporosis in this patient.

Adrenal Cortex↗

PubMed1990

Developmentally regulated expression of an exon containing a stop codon in the gene for glutamic acid decarboxylase.

In the adult rat brain, the gene for glutamic acid decarboxylase (GAD; L-glutamate 1-carboxy-lyase, EC 4.1.1.15) is expressed predominantly as a 3.7-kilobase transcript. Earlier data showed that embryonic brain expresses an RNA transcript distinct from the adult form; however, the exact structure of this form was not elucidated. Here, transcripts expressed in the embryonic but not the adult brain were cloned and analyzed. These transcripts include an exon not expressed in the adult inserted into coding sequence. The embryonic exon contains a stop codon that is in-frame with the coding sequence. The exon is found in genomic DNA within the GAD gene where it is flanked by introns with conventional splice sites. On the basis of these structural data, we propose the hypothesis that, early in brain development, transcripts encoding a truncated form of GAD are expressed. The deduced protein cannot function as a decarboxylase because the stop codon in the embryonic exon occurs upstream of the binding site for pyridoxal phosphate, an essential cofactor. Thus, alternative splicing plays a crucial role in the pathway leading to the development of functional GABAergic neurons. The central nervous system-derived cell lines B65 and C6 express a mixture of the adult and embryonic forms of GAD mRNA. They therefore are useful clonal models of central nervous system cells in the early phases of differentiation.

Age Factors↗

PubMed1988

Thyroid hormone modulates the introduction of a stop codon in rat liver apolipoprotein B messenger RNA.

Apolipoprotein B (apoB) biosynthesis by rat liver was studied following thyroid hormone (3,5,3'-triiodo-L-thyronine) administration to hypothyroid rats. Pharmacologic doses of 3,5,3'-triiodo-L-thyronine caused suppression of apoB100 synthesis but did not affect apoB48 levels. There was no detectable apoB100 synthesis in hyperthyroid rats. To examine whether these results were mediated by the previously demonstrated mechanism of RNA modification (Powell, L. M., Wallis, S. C., Pease, R. J., Edwards, Y. H., Knott, T. J., and Scott, J. (1987) Cell 50, 831-840), the DNA sequence corresponding to the C-terminal end of rat apoB48 was determined from rat liver cDNA clones. Rat cDNAs contained a stop codon at an identical position to that found in human and rabbit apoB48 intestinal cDNA. To quantitate the relative amounts of apoB100 and apoB48 message, cDNA was synthesized from hepatic and intestinal apoB RNA and a 207-base pair fragment amplified using the polymerase chain reaction. The products were then differentially hybridized with oligonucleotides specific for apoB100 (containing CAA) or apoB48 (TAA). Control and hypothyroid liver contained approximately equal amounts of CAA and TAA, while hyperthyroid liver contained greater than 90% TAA. All gut samples contained 94-98% TAA. Genomic DNA from rat liver contained only CAA. The results demonstrate that apoB mRNA modification can be hormonally modulated in the adult rat by induction of a mechanism involving substitution of a stop codon into hepatic apoB100 mRNA.

Animals↗

PubMed1992

No stop codons in the antisense strands of the genes for nylon oligomer degradation.

Genes for nylon oligomer-degrading enzymes are unique in the sense that the enzymes encoded by them are found not to have any appropriate substrates during most of the period of their evolution. Furthermore, these nylB genes form a family not related to any other known gene families. The base sequences of these genes were examined and a common characteristic was found: a long stretch of sequence without chain-terminating base triplets, defined as a nonstop frame (NSF), is being maintained on the antisense strand. Moreover, a certain coding frame is open for both the sense and the antisense sequences, while the other frames have many stop codons. The probability of the presence of these NSFs on the antisense strand of a gene is very small (0.0001-0.0018). In addition, another gene for nylon oligomer degradation was found to have a NSF on its antisense strand, and this gene is phylogenically independent of the nylB genes. Therefore, the presence of these NSFs is very rare and improbable. Even if the common ancestral gene of the nylB family was originally endowed with a NSF on its antisense strand, the probability of this original NSF persisting in one of its descendants of today is only 0.007. Unless an unknown force was maintaining the NSF, it would have quickly disappeared by random emergences of chain terminators. Therefore, the presence of such rare NSFs on all three antisense strands of the nylB gene family suggests that there is some special mechanism for protecting these NSFs from mutations that generate the stop codons. Such a mechanism may enable NSFs to evolve into new functional genes and hence seems to be a basic mechanism for the birth of new enzymes.

Amidohydrolases↗

PubMed1990

Rapid detection and further characterization of infection with hepatitis B virus variants containing a stop codon in the distal pre-C region.

Recently, hepatitis B virus (HBV) replication in the absence of HBe antigenaemia has been attributed to HBV variants with a TAG stop codon in the distal pre-C region associated with one or two point mutations. We describe here a rapid detection method for the diagnosis of such HBeAg-negative HBV variants using selective oligonucleotide hybridization. The entire pre-C region was amplified by the polymerase chain reaction and hybridized under stringent conditions with non-mutated (M0), one (M1) and two (M2) point-mutated oligonucleotide probes. Of the 15 HBeAg-positive (group I) and 20 HBeAg-negative (group II) serum samples studied, 14 samples in group I and one sample in group II hybridized with M0 only and 18 samples in group II hybridized with M1 or M2, or both. The remaining two samples (from groups I and II, respectively) failed to hybridize with any of the three probes. DNA sequencing confirmed mixed distal pre-C sequences in samples hybridizing with more than one probe and also revealed novel mutations in the distal pre-C region of the two samples which failed to hybridize with any of the probes. The latter sample had a +2 frameshift and hence represented a new type of HBeAg-negative HBV variant. This method may therefore prove useful in the diagnosis of infections by HBeAg-negative HBV variants resulting from common mutations in the pre-C region, as well as for the identification of less common variants with novel mutations in the same region.

Base Sequence↗

PubMed1990

Frameshifting at the internal stop codon within the mRNA for bacterial release factor-2 on eukaryotic ribosomes.

A translational frameshift is necessary in the synthesis of Escherichia coli release factor 2 (RF-2) to bypass an in-frame termination codon within the coding sequence. High-efficiency frameshifting around this codon can occur on eukaryotic ribosomes as well as prokaryotic ribosomes. This was determined from the relative efficiency of translation of RF-2 RNA compared with that for the other release factor RF-1, which lacks the in-frame premature stop codon. Since the termination product is unstable an absolute measure of the efficiency of frameshifting has not been possible. A gene fusion between trpE and RF-2 was carried out to give a stable termination product as well as the frameshift product, thereby allowing a direct determination of frameshifting efficiency. The extension of RF-2 RNA near its start codon with a fragment of the trpE gene, while still allowing high efficiency frameshifting on prokaryotic ribosomes, surprisingly gives a different estimate of frameshifting on the eukaryotic ribosomes than that obtained with RF-2 RNA alone. This paradox may be explained by long distance context effects on translation rates in the frameshift region created by the trpE sequences in the gene fusion, and may reflect that pausing and translation rate are fundamental factors in determining the efficiency of frameshifting.

Base Sequence↗

PubMed1992

The intronless mouse gene for the tissue specific splicing protein SmN is a processed pseudogene containing a stop codon after thirty-one amino acids.

The SmN protein is a component of small ribonucleoprotein particles which is closely related to the ubiquitously expressed splicing proteins SmB and B' but is expressed in only a small number of cells and tissues. We have isolated a mouse SmN-related sequence which lacks introns and contains multiple changes from the SmN cDNA sequence including a stop codon after thirty-one amino acids which would prevent it encoding functional SmN protein. This indicates that this intronless gene is a processed pseudogene and that the functional gene has yet to be isolated. In agreement with this southern blotting of mouse DNA with SmN probes reveals bands, additional to those derived from the pseudogene, which are characteristic of an intron-containing SmN gene. The relationship of the pseudogene to the functional SmN gene and to an intronless SmN-related sequence in the rat genome is discussed.

Amino Acid Sequence↗

PubMed1988

A homozygous point mutation results in a stop codon in the C1q B-chain of a C1q-deficient individual.

Southern blot analysis of the B-chain genes in one of eight C1q-deficient individuals revealed an abnormal banding pattern. The defect, which was homozygous, could be localized by restriction mapping to a single Taq I site within residue 150 in the coding region of the B-chain gene. DNA sequencing across the site revealed a stop codon that would cause premature termination of the protein product. No material corresponding to the A or C chains, or a truncated B chain, could be identified by antigenic analysis of the patient's serum, indicating that a complete B chain is required for secretion of a C1q molecule.

Codon↗

PubMed1985

An active variant of the prokaryotic transposable element IS903 carries an amber stop codon in the middle of an open reading frame.

The prokaryotic mobile genetic element IS903.B is an active variant of IS903. It differs from IS903 and IS102 by 34 and 61 nucleotide substitutions, respectively. The large open reading frame (ORFI) which probably encodes the transposase is conserved in all three IS elements, whereas the smaller open reading frame (ORFII), which codes on the opposite DNA strand and entirely overlaps ORFI, contains an amber stop codon past the middle of ORFII in IS903.B. Experiments using Escherichia coli K12 strains permissive or non-permissive for amber mutations revealed no difference in the cointegration frequency mediated by IS903.B. Therefore, a possible peptide encoded by ORFII on the IS903-related element is unlikely to be necessary for transposition.

Base Sequence↗