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C Transition (c + transition)
Selected AbstractsA model for targeted substitution mutagenesis during SOS replication of double-stranded DNA containing cis-syn cyclobutane thymine dimersENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 9 2006Helen A. Grebneva Abstract A model for ultraviolet mutagenesis is described that is based on the formation of rare tautomeric bases in pyrimidine dimers. It is shown that during SOS synthesis the modified DNA-polymerase inserts canonical bases opposite the dimers; the inserted bases are capable of forming hydrogen bonds with bases in the template DNA. SOS-replication of double-stranded DNA having thymine dimers, with one or both bases in a rare tautomeric conformation, results in targeted transitions, transversions, or one-nucleotide gaps. Structural analysis indicates that one type of dimer containing a single tautomeric base (TT1*, with the "*" indicating a rare tautomeric base and the subscript referring to the particular conformation) can cause A:T , G:C transition or homologous A:T , T:A transversion, while another dimer (TT2*) can cause a one-nucleotide gap. The dimers containing T4* result in A:T , C:G transversion, while TT5* dimers can cause A:T , C:G transversion or homologous A:T , T:A transversion. If both bases in the dimer are in a rare tautomeric form, then tandem mutations or double-nucleotide gaps can be formed. The dimers containing the rare tautomeric forms T1 *,, T2*,, T3*,, T4*,, and T5*, may not result in mutations. The question of whether dimers containing T4*, and T5*, result in mutations requires further investigation. Environ. Mol. Mutagen., 2006. © 2006 Wiley-Liss, Inc. [source] Identification of a novel mutation in keratin 1 in a family with epidermolytic hyperkeratosisEXPERIMENTAL DERMATOLOGY, Issue 1 2000M. J. Arin Abstract: Epidermolytic hyperkeratosis (EHK) is a hereditary skin disorder typified by blistering due to cytolysis. One in 100,000 individuals is affected by this autosomal-dominant disease. The onset of the disease phenotype is typically at birth. Histological and ultrastructural examination of the epidermis shows a thickened stratum corneum and tonofilament clumping around the nucleus of suprabasal keratinocytes. Linkage studies localized the disease genes on chromosomes 12q and 17q which contain the type II and type I keratin gene clusters. Recently, several point mutations in the genes encoding the suprabasal keratins, K1 and K10, have been reported in EHK patients. We have investigated a large kindred affected by EHK and identified a new point mutation in the 2B region of keratin 1 (I107T), resulting from a T to C transition in codon 478. [source] Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect,,HUMAN MUTATION, Issue 3 2003Carina M. Rivolta Abstract Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine. We analyzed the TPO gene in 14 unrelated patients with clinical evidence of iodide organification defects. Seven of the affected individuals harbored mutations in the TPO gene; one was compound heterozygous, the others were simply heterozygous for TPO mutations. Five novel mutations have been identified, one of which was found to be a single nucleotide deletion, while the other four were single nucleotide substitutions. A frameshift mutation c.387delC was detected in exon 5 which leads to an early termination signal in exon 7 (p.N129fsX208). Two missense mutations were identified in exon 8. The first, a c.920A>C transversion that results in a p.N307T substitution, was found in two patients. The second, a c.1297G>A transition, results in p.V433M. A c.1496C>T transition was detected in exon 9 that caused the substitution p.P499L. Finally, in exon 14 a c.2422T>C transition was identified, causing a p.C808R change. In addition, the previously reported GGCC duplication in exon 8 (c.1186underscore;1187insGGCC; p.R396fsX472) was also detected in two affected individuals, one of whom was a compound heterozygous (p.R396fsX472/p.V433M). © 2003 Wiley-Liss, Inc. [source] Identification of novel single nucleotide polymorphisms within the NOTCH4 gene and determination of association with MHC allelesINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 2 2003R. Tazi-Ahnini Summary Mapping of disease susceptibility loci within the MHC has been partly hampered by the high degree of polymorphism of the HLA genes and the high level of linkage disequilibrium (LD) between markers within the MHC region. It is therefore important to identify new markers and determine the level of LD between HLA alleles and non-HLA genes. The NOTCH4 gene lies at the centromeric end of the MHC class III region, approximately 335 kb telomeric of the DRB1 locus. The encoded protein is an oncogene that is important in regulating vascular development and remodelling. A recent report has linked polymorphisms within NOTCH4 with risk of developing schizophrenia. We have investigated if coding polymorphisms exist within this gene and have identified three single nucleotide polymorphisms; a synonomous T to C transition at +1297 (HGBASE accession number SNP000064386), a synonomous A to G transition at +3061 (SNP000064387) and an A to G transition at +3063 which results in a replacement of glycine with aspartic acid at amino acid 279 (SNP000064388). The allele frequencies of +1297T, +3061A and +3063G were 0.65, 0.66 and 0.66, respectively. Linkage disequilibrium was detected both between these markers and with MHC alleles. These findings can be used in the fine mapping of disease susceptibility alleles within the MHC. [source] The polymorphism of transforming growth factor-,1 gene in Japanese patients with systemic sclerosisBRITISH JOURNAL OF DERMATOLOGY, Issue 3 2002T. Ohtsuka Summary Background Transforming growth factor (TGF)-, has been shown to be a potent stimulator of collagen production by fibroblasts, and could play a role in the pathogenesis of systemic sclerosis (SSc). Objectives To study the possible involvement of TGF-,1 gene polymorphism in Japanese patients with SSc. Methods Fifty-nine patients with SSc and 110 normal subjects were studied. Genomic DNA was extracted from skin tissues, and was amplified in a thermal cycler, generating a TGF-,1 gene fragment with a size of 294 bp. The T to C transition at T869C (Leu10Pro) and the G to C transition at G915C (Arg25Pro) were identified by digestion with MspA1I and BglI, respectively. Results At T869C (Leu10Pro), the frequency of the C allele in SSc (65·3%) was significantly higher than in normal controls (50·5%) (P < 0·01). SSc showed C/C allele 42·4%, C/T 45·8% and T/T 11·2%. Normal controls showed C/C allele 26·4%, C/T 48·2% and T/T 25·5%. The frequency of the C/C allele in SSc was significantly higher than in normal controls, in comparison with the T/T allele (P < 0·02), but no significant difference was found between the frequency of the C/C allele vs. the C/T allele. The frequency of the C/C allele showed no significant difference between diffuse and limited SSc. At G915C (Arg25Pro), all the normal controls and SSc patients showed only the G/G allele. These results are different from a previous study in which the frequency of the T/T allele was high in SSc at T869C (Leu10Pro). Conclusions This discrepancy may indicate that Japanese patients with SSc show a different genetic predisposition to TGF-,1. [source] A novel mutation in the mitochondrial tRNA for tryptophan causing a late-onset mitochondrial encephalomyopathyACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010P. S. Sanaker Sanaker PS, Nakkestad HL, Downham E, Bindoff LA. A novel mutation in the mitochondrial tRNA for tryptophan causing a late-onset mitochondrial encephalomyopathy. Acta Neurol Scand: 2010: 121: 109,113. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Background,,, Mitochondrial DNA (mtDNA) mutations are increasingly being recognized as causes of late-onset disease. We report a patient with a late-onset mitochondrial encephalomyopathy caused by a novel G > C transition in mtDNA at position 5556 in the gene encoding the tRNA for tryptophan (MTTW). Aims,,, To investigate the cause of disease and assess the pathogenicity of this new mutation. Methods,,, Clinical, histopathological and gene sequencing studies. Quantification of the mutation was performed in different tissues from the patient and two relatives and in single muscle fibres. Results,,, The mutation was heteroplasmic, segregated in biochemically affected muscle fibres and was absent in blood. The level of mutation in skeletal muscle was higher than in brain, although the brain was clinically the most affected tissue. Discussion,,, The 5556G > C mutation appears sporadic. It was not found in any of the family members tested, although some of them manifested disorders that can be associated with mtDNA disease. In addition to reporting the eighth mutation in MTTW, our case illustrates the challenges posed when assigning pathogenicity to mtDNA mutations. [source] A novel keratin 9 gene mutation (Asn160His) in a Taiwanese family with epidermolytic palmoplantar keratodermaCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 3 2004J.-H. Lin Summary Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited disorder of keratinization. Recent molecular studies have shown that EPPK is caused by mutations in keratin 9 gene (KRT9). We report a Taiwanese family with EPPK with a novel mutation with an A,C transition at the first nucleotide of codon 160 in KRT9. The mutation is predicted to result in an asparagine to histidine substitution (N160H) at the beginning of the ,-helical 1A domain of keratin 9. Mutations in this region could disrupt keratin filament assembly, leading to degeneration or cytolysis of keratinocytes. Our mutation analysis confirms that codon 160 in KRT9 is one of the mutation hot spots in EPPK. [source] Photomutagenicity of thiabendazole, a postharvest fungicide, in bacterial assaysENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2003Mie Watanabe-Akanuma Abstract We investigated the photomutagenicity of thiabendazole (TBZ), a postharvest fungicide commonly used on imported citrus fruits. Using UVA light (320,400 nm), we irradiated bacterial cultures with or without TBZ in a 24-well multiplate. UVA-irradiation without TBZ was not mutagenic to the tester strains, nor was unirradiated TBZ. TBZ was strongly photomutagenic in Escherichia coli WP2uvrA and WP2uvrA/pKM101 strains, weakly photomutagenic in Salmonella typhimurium TA100 and TA98, and not photomutagenic in S. typhimurium TA1535 and TA1538. The photomutagenicity of TBZ was more evident in WP2uvrA/pKM101, which carries the trpE65 ochre mutation (TAA), than in TA100, which carries the hisG46 missense mutation (CCC). In E. coli WP3101,WP3106 and the corresponding pKM101-containing strains, photoactivated TBZ induced predominantly G:C,A:T transitions and A:T,T:A transversions. In the plasmid-containing strains only, TBZ induced a moderate number of A:T,G:C transitions and a few A:T,C:G and G:C,T:A transversions. The observation that UVA-irradiated TBZ mutated both G:C and A:T basepairs may explain why WP2uvrA/pKM101 was more sensitive to its mutagenicity than TA100. TBZ that was irradiated before it was added to the WP2uvrA/pKM101 cells was not photomutagenic, which suggests that the photomutagenic products of TBZ were unstable or rapidly reacted with other molecules before being incorporated into cells. Environ. Mol. Mutagen. 41:92,98, 2003. © 2003 Wiley-Liss, Inc. [source] | |||||||||||||