Search results for "Codon"

2020

The efficiency of chemotherapy drugs can be affected by ATP-binding cassette (ABC) transporter expression or by their mutation status. Multidrug resistance is linked with ABC transporter overexpression. In the present study, we performed rare mutation analyses for 12 ABC transporters related to drug resistance (ABCA2, -A3, -B1, -B2, -B5, -C1, -C2, -C3, -C4, -C5, -C6, -G2) in a dataset of 18 cancer patients. We focused on rare mutations resembling tumor heterogeneity of ABC transporters in small tumor subpopulations. Novel rare mutations were found in ABCC1, but not in the other ABC transporters investigated. Diverse ABCC1 mutations were found, including nonsense mutations causing premature …

A nonsense mutation abrogates production of a functional enterotoxin A in Clostridium difficile toxinotype VIII strains of serogroups F and X.

1999

Clostridium difficile strains of toxinotype VIII from serogroups F and X are described as toxin B-positive, toxin A-negative (TcdB+ A-), although they harbour almost the entire tcdA gene. To identify the reason for the lack of TcdA detection, we analyzed catalytic and ligand domains of TcdA-1470 of the type strain of serogroup F, strain 1470. Using recombinant fragments, the C-terminal immunodominant ligand domain TcdA3-1470, spanning amino acid residues 1694-2711 (corresponding to VPI 10463 sequence), was detected in Western blots. Similar experiments using the recombinant N-terminal catalytic fragment TcdAc1-2-1470 (amino acid positions 1-544) failed. In addition, this fragment showed no …

Taxas de substituições das Annonaceas: uma perspectiva do modelo códon

2014

The Annonaceae includes cultivated species of economic interest and represents an important source of information for better understanding the evolution of tropical rainforests. In phylogenetic analyses of DNA sequence data that are used to address evolutionary questions, it is imperative to use appropriate statistical models. Annonaceae are cases in point: Two sister clades, the subfamilies Annonoideae and Malmeoideae, contain the majority of Annonaceae species diversity. The Annonoideae generally show a greater degree of sequence divergence compared to the Malmeoideae, resulting in stark differences in branch lengths in phylogenetic trees. Uncertainty in how to interpret and analyse these…

The fitness effects of synonymous mutations in DNA and RNA viruses.

2011

Despite being silent with respect to protein sequence, synonymous nucleotide substitutions can be targeted by natural selection directly at the DNA or RNA level. However, there has been no systematic assessment of how frequent this type of selection is. Here, we have constructed 53 single random synonymous substitution mutants of the bacteriophages Qb and UX174 by site-directed mutagenesis and assayed their fitness. Analysis of this mutant collection and of previous studies undertaken with a variety of single-stranded (ss) viruses demonstrates that selection at synonymous sites is stronger in RNA viruses than in DNA viruses. We estimate that this type of selection contributes approximately …

P53 gene codon 72 polymorphism in patients with oral squamous cell carcinoma in the population of northern Iran.

2014

Objectives: Squamous cell carcinoma is the most common cancer of the oral cavity, and several etiologic factors are involved in its development. Single nucleotide polymorphism (SNP) of the P 53 gene codon 72 ( P 53c72) changes the structure of the protein and affects its activity. The prevalence of P 53c72 different genotypes, which seems to vary with race and geographic location, has shown a strong correlation with many types of human cancers. The aim of this study was to investigate the correlation between P 53c72 polymorphism and risk of oral squamous cell carcinoma (OSCC) in the heavily populated Gilan Province in northern Iran. Design of S tudy: This case-control study was done on 55 p…

Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatell…

2006

Background: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. Patients and methods: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The fre…

Beneficial Read-Through of aUSH1CNonsense Mutation by Designed Aminoglycoside NB30 in the Retina

2010

PURPOSE. The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. USH is clinically and genetically heterogeneous, assigned to three clinical types. The most severe type is USH1, characterized by profound inner ear defects and retinitis pigmentosa. Thus far, no effective treatment for the ophthalmic component of USH exists. The p.R31X nonsense mutation in USH1C leads to a disease causing premature termination of gene translation. Here, we investigated the capability of the novel synthetic aminoglycoside NB30 for the translational read-through of the USH1C-p.R31X nonsense mutation as a retinal therapy option. METHODS. Read-through of p.R31X by three com…

Nonsense codons suppression. An acute toxicity study of three optimized TRIDs in murine model, safety and tolerability evaluation.

2022

Stop mutations cause 11% of the genetic diseases, due to the introduction of a premature termination codon (PTC) in the mRNA, followed by the production of a truncated protein. A promising therapeutic approach is the suppression therapy by Translational Readthrough Inducing Drugs (TRIDs), restoring the expression of the protein. Recently, three new TRIDs (NV848, NV914, NV930) have been proposed, and validated by several in vitro assays, for the rescue of the CFTR protein, involved in Cystic Fibrosis disease. In this work, an acute toxicological study for the three TRIDs was conducted in vivo on mice, according to the OECD No.420 guidelines. Animals were divided into groups and treated with …

Intra-specific variability and biological relevance of P3N-PIPO protein length in potyviruses

2013

Background:Pipo was recently described as a new ORF encoded within the genome of the Potyviridae family members (PNAS 105:5897-5902, 2008). It is embedded within the P3 cistron and is translated in the +2 reading frame relative to the potyviral long ORF as the P3N-PIPO fusion protein. In this work, we first collected pipo nucleotide sequences available for different isolates of 48 Potyvirus species. Second, to determine the biological implications of variation in pipo length, we measured infectivity, viral accumulation, cell-to-cell and systemic movements for two Turnip mosaic virus (TuMV) variants with pipo alleles of different length in three different susceptible host species, and tested…

Glutamine Codon Usage and polyQ Evolution in Primates Depend on the Q Stretch Length

2018

Abstract Amino acid usage in a proteome depends mostly on its taxonomy, as it does the codon usage in transcriptomes. Here, we explore the level of variation in the codon usage of a specific amino acid, glutamine, in relation to the number of consecutive glutamine residues. We show that CAG triplets are consistently more abundant in short glutamine homorepeats (polyQ, four to eight residues) than in shorter glutamine stretches (one to three residues), leading to the evolutionary growth of the repeat region in a CAG-dependent manner. The length of orthologous polyQ regions is mostly stable in primates, particularly the short ones. Interestingly, given a short polyQ the CAG usage is higher in…