Search results for " Mutation"
showing 10 items of 1212 documents
Novel form of X-linked nonsyndromic hearing loss with cochlear malformation caused by a mutation in the type IV collagen gene COL4A6
2013
Hereditary hearing loss is the most common human sensorineural disorder. Genetic causes are highly heterogeneous, with mutations detected in >40 genes associated with nonsyndromic hearing loss, to date. Whereas autosomal recessive and autosomal dominant inheritance is prevalent, X-linked forms of nonsyndromic hearing impairment are extremely rare. Here, we present a Hungarian three-generation family with X-linked nonsyndromic congenital hearing loss and the underlying genetic defect. Next-generation sequencing and subsequent segregation analysis detected a missense mutation (c.1771G>A, p.Gly591Ser) in the type IV collagen gene COL4A6 in all affected family members. Bioinformatic analysis an…
Clinical, molecular and functional characterization of two novel mutations associated to compound heterozygous FHBL
2012
Introduction. Primary hypobetalipoproteinemia (pHBL) is a monogenic heterogeneous condition characterized by total cholesterol (TC) and/or LDL cholesterol (LDL-C) levels below the 5th percentile of the reference population. Heterozygous APOB gene mutations are responsible for the majority of the dominant pHBL causing the familial hypobetalipoproteinemia (FHBL). The clinical phenotype of heterozygous FHBL is usually mild. The homozygous or compound heterozygous APOB mutations are in some cases responsible for a more severe biochemical and clinical phenotype, similar to the abetalipoproteinemia (ABL) due to homozygous mutations in the MTP gene, characterized by intestinal malabsorption, pigme…
An Analysis of the Influence of Noneffective Instructions in Linear Genetic Programming
2020
Abstract Linear Genetic Programming (LGP) represents programs as sequences of instructions and has a Directed Acyclic Graph (DAG) dataflow. The results of instructions are stored in registers that can be used as arguments by other instructions. Instructions that are disconnected from the main part of the program are called noneffective instructions, or structural introns. They also appear in other DAG-based GP approaches like Cartesian Genetic Programming (CGP). This article studies four hypotheses on the role of structural introns: noneffective instructions (1) serve as evolutionary memory, where evolved information is stored and later used in search, (2) preserve population diversity, (3)…
Parallelizing Epistasis Detection in GWAS on FPGA and GPU-Accelerated Computing Systems
2015
This is a post-peer-review, pre-copyedit version of an article published in IEEE - ACM Transactions on Computational Biology and Bioinformatics. The final authenticated version is available online at: http://dx.doi.org/10.1109/TCBB.2015.2389958 [Abstract] High-throughput genotyping technologies (such as SNP-arrays) allow the rapid collection of up to a few million genetic markers of an individual. Detecting epistasis (based on 2-SNP interactions) in Genome-Wide Association Studies is an important but time consuming operation since statistical computations have to be performed for each pair of measured markers. Computational methods to detect epistasis therefore suffer from prohibitively lon…
Boolean Networks: A Primer
2021
Abstract Autism Spectrum Disorders (ASDs) stand out as a relevant example where omics-data approaches have been extensively and successfully employed. For instance, an outstanding outcome of the Autism Genome Project relies in the identification of biomarkers and the mapping of biological processes potentially implicated in ASDs’ pathogenesis. Several of these mapped processes are related to molecular and cellular events (e.g., synaptogenesis and synapse function, axon growth and guidance, etc.) that are required for the development of a correct neuronal connectivity. Interestingly, these data are consistent with results of brain imaging studies of some patients. Despite these remarkable pr…
Molecular architecture of a toxin pore: a 15-residue sequence lines the transmembrane channel of staphylococcal alpha-toxin.
1996
Staphylococcus aureus alpha-toxin is a hydrophilic polypeptide of 293 amino acids that produces heptameric transmembrane pores. During assembly, the formation of a pre-pore precedes membrane permeabilization; the latter is linked to a conformational change in the oligomer. Here, 41 single-cysteine replacement toxin mutants were thiol-specifically labelled with the polarity-sensitive fluorescent probe acrylodan. After oligomerization on membranes, only the mutants with acrylodan attached to residues in the sequence 118-140 exhibited a marked blue shift in the fluorescence emission maximum, indicative of movement of the fluorophore to a hydrophobic environment. Within this region, two functio…
Mutation Analysis of Core Binding Factor A1 in Patients with Cleidocranial Dysplasia
1999
SummaryCleidocranial dysplasia (CCD) is a dominantly inherited disorder characterized by patent fontanelles, wide cranial sutures, hypoplasia of clavicles, short stature, supernumerary teeth, and other skeletal anomalies. We recently demonstrated that mutations in the transcription factor CBFA1, on chromosome 6p21, are associated with CCD. We have now analyzed the CBFA1 gene in 42 unrelated patients with CCD. In 18 patients, mutations were detected in the coding region of the CBFA1 gene, including 8 frameshift, 2 nonsense, and 9 missense mutations, as well as 2 novel polymorphisms. A cluster of missense mutations at arginine 225 (R225) identifies this residue as crucial for CBFA1 function. …
A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma.
1995
A mutated cyclin-dependent kinase 4 (CDK4) was identified as a tumor-specific antigen recognized by HLA-A2. 1-restricted autologous cytolytic T lymphocytes (CTLs) in a human melanoma. The mutated CDK4 allele was present in autologous cultured melanoma cells and metastasis tissue, but not in the patient's lymphocytes. The mutation, an arginine-to-cysteine exchange at residue 24, was part of the CDK4 peptide recognized by CTLs and prevented binding of the CDK4 inhibitor p16INK4a, but not of p21 or of p27KIP1. The same mutation was found in one additional melanoma among 28 melanomas analyzed. These results suggest that mutation of CDK4 can create a tumor-specific antigen and can disrupt the ce…
Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.
2015
Abstract Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importanc…
Bleomycin genotoxicity alteration by glutathione and cytochrome P-450 cellular content in respiratory proficient and deficient strains of Saccharomyc…
1999
The genotoxic effects of the antiblastic drug bleomycin were studied in the D7 strain of Saccharomyces cerevisiae and on its derivative mitochondrial mutant rho degree at different cellular concentrations of two drug metabolizing systems, glutathione (GSH) and cytochrome P-450. Bleomycin mutagenic activity was evaluated as frequencies of mitotic gene conversion, reversion and total aberrations under different physiological conditions. In the D7 strain, petite mutant induction was also detected. This is important due to the role of the mitochondrial genome in cancer induction, ageing and degenerative diseases. Both strains showed higher convertant than revertant induction. At high cytochrome…