Search results for "Stop codon"
showing 10 items of 43 documents
A frame shift mutation in a hot spot region of the nuclear autoantigen La (SS-B).
1996
A hot spot region was identified in the exon 7 of the nuclear autoantigen La (SS-B). Two La cDNAs were identified which contained a frame shift mutation in the hot spot region. One La cDNA was isolated from a cDNA library made from peripheral blood lymphocytes of an autoimmune patient with primary Sjogren's Syndrome, the other La cDNA was isolated from a human liver cDNA library. The patient's La cDNA had a deletion and the liver La cDNA had an insert of an (A)-residue at the same position. Inserts of 4, 16 and 24 more or less homogeneous (A)-residues were found at the same site in the three La retropseudogenes. The hot spot region located in one of the major autoepitope regions of the La a…
Toward a Rationale for the PTC124 (Ataluren) Promoted Readthrough of Premature Stop Codons: A Computational Approach and GFP-Reporter Cell-Based Assay
2014
The presence in the mRNA of premature stop codons (PTCs) results in protein truncation responsible for several inherited (genetic) diseases. A well-known example of these diseases is cystic fibrosis (CF), where approximately 10% (worldwide) of patients have nonsense mutations in the CF transmembrane regulator (CFTR) gene. PTC124 (3-(5-(2-fluorophenyl)-1,2,4-oxadiazol-3-yl)-benzoic acid), also known as Ataluren, is a small molecule that has been suggested to allow PTC readthrough even though its target has yet to be identified. In the lack of a general consensus about its mechanism of action, we experimentally tested the ability of PTC124 to promote the readthrough of premature termination c…
Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression.
1993
Abstract The fourth component of the human complement system (C4) is coded for by two genes, C4A and C4B, located within the MHC. Null alleles of C4 (C4Q0) are defined by the absence of C4 protein in plasma. These null alleles are due either to large gene deletions or to nonexpression of the respective genes. In a previous study, evidence was obtained for nonexpressed defective genes at the C4A locus, and for gene conversion at the C4B locus. To further characterize the molecular basis of these non-expressed C4A genes, we selected nine pairs of PCR primers from flanking genomic intron sequences to amplify all 41 exons from individuals with a defective C4A gene. The amplified products were s…
Statistical analysis of yeast genomic downstream sequences reveals putative polyadenylation signals
2000
The study of a few genes has permitted the identification of three elements that constitute a yeast polyadenylation signal: the efficiency element (EE), the positioning element and the actual site for cleavage and polyadenylation. In this paper we perform an analysis of oligonucleotide composition on the sequences located downstream of the stop codon of all yeast genes. Several oligonucleotide families appear over-represented with a high significance (referred to herein as"words"). The family with the highest over-representation includes the oligonucleotides shown experimentally to play a role as EEs. The word with the highest score is TATATA, followed, among others, by a series of singl…
Inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase as possible mechanism to readthrough premature termination codons (UGAs) of th…
2022
Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10 % of the mutations affecting the CFTR gene are "stop" mutations, which generate a Premature Termination Codon (PTC), thus resulting in the synthesis of a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, that is the capacity of the ribosome to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough and for some of them the mechanism of action is still under debate. By in silico analysis as well as in vitro studies, we investigate a possible mechanism of action (MOA) by whic…
Mutations Involving the Transcription Factor CBFA1 Cause Cleidocranial Dysplasia
1997
AbstractCleidocranial dysplasia (CCD) is an autosomal-dominant condition characterized by hypoplasia/aplasia of clavicles, patent fontanelles, supernumerary teeth, short stature, and other changes in skeletal patterning and growth. In some families, the phenotype segregates with deletions resulting in heterozygous loss of CBFA1, a member of the runt family of transcription factors. In other families, insertion, deletion, and missense mutations lead to translational stop codons in the DNA binding domain or in the C-terminal transactivating region. In-frame expansion of a polyalanine stretch segregates in an affected family with brachydactyly and minor clinical findings of CCD. We conclude th…
Automatic simulation of RNA editing in plants for the identification of novel putative Open Reading Frames
2017
In plant mitochondria an essential mechanism for gene expression is RNA editing, often influencing the synthesis of functional proteins. RNA editing alters the linearity of genetic information transfer, intro- ducing differences between RNAs and their coding DNA sequences that hind both experimental and computational research of genes. Thus common software tools for gene search, successfully exploited to find canonic genes, often can fail in discovering genes encrypted in the genome of plants. In this work we propose a novel strategy useful to intercept candidate coding sequences resulting from some possible editing substitutions on the start and stop codons of a given input organism DNA. O…
Forced Retroevolution of an RNA Bacteriophage
2000
AbstractThe operator hairpin ahead of the replicase gene in RNA bacteriophage MS2 contains overlapping signals for binding the coat protein and ribosomes. Coat protein binding inhibits further translation of the gene and forms the first step in capsid formation. The hairpin sequence was partially randomized to assess the importance of this structure element for the bacteriophage and to monitor alternative solutions that would evolve on the passaging of mutant phages. The evolutionary reconstruction of the operator failed in the majority of mutants. Instead, a poor imitation developed containing only some of the recognition signals for the coat protein. Three mutants were of particular inter…
A method to isolate cDNA-quality RNA from adult conifer needles and a psbA cDNA from Norway spruce
1996
Summary In order to investigate the expression of the psbA gene in damaged and undamaged Norway spruce trees ( Picea abies ) a cDNA clone encoding the D1 protein was isolated via RT-PCR. Applying a method developed by Schneiderbauer et al. (1991) with some modifications, we were able to obtain the required RNA from mature needles and successfully reverse transcribe it into cDNA. Sequence analysis of the cDNA clone revealed an open reading frame (ORF) encoding a 353 amino acid polypeptide that is highly homologous to the D1 protein sequences deduced from higher plant psbA genes. A 4 bp insertion, directly following the stop codon ochre (TAA), was found by comparison with two Pinus species, t…
Epidemiological study of nonsyndromic hearing loss in Sicilian newborns
2007
Deafness is caused by a variety of facts, genetic and environmental. Regarding the acquired causes, deafness can be the consequence of prenatal infections, acoustic or cerebral trauma, and the use of ototoxic drugs. Deafness can be the only manifestation (nonsyndromic forms) or it may occur together with other phenotypic findings (syndromic forms). The majority of nonsyndromicdeafness has a genetic basis [Van Camp et al., 1997]. In recent years, deafness and hearing loss have assumed a clinical importance in the study of congenital disorders [Morton et al., 1991]. The clinical interest for hearing loss is supported by the social impact that this disorder has; if not treated, delays in the d…