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Nucleotide Mutations (nucleotide + mutation)
Kinds of Nucleotide Mutations Selected AbstractsAssociation Study Between Genetic Polymorphisms in the 14,3-3 , Chain and Dopamine D4 Receptor Genes and AlcoholismALCOHOLISM, Issue 3 2000H. Ishiguro Background: The dopaminergic system may be involved in the development of alcoholism. As part of our ongoing studies on the association between alcoholism and dopaminergic genes, we report herein a mutation analysis of the 14,3-3 , chain gene (YWHAH) and an association study between alcoholism and the YWHAH and dopamine D4 receptor gene (DRD4) polymorphisms. Methods: Nucleotide mutations were investigated using single-strand conformation polymorphism methods. Associations were analyzed using a case-control design involving 185 Japanese alcoholics and 286 Japanese controls. Results: Five polymorphisms, -147G>A, -134(GCCTGCA)2,4, IVS1+31(G)7,8. IVS1+73,74ins(G), and 753A>G, were detected on the YWHAH, and three of them were novel. No significant associations were found between alcoholism and these polymorphisms or two additional polymorphisms on DRD4 exon III and DRD4 -521C/T. Conclusions: YWHAH and DRD4 do not appear to play a major role in the development of alcoholism. [source] Identification and characterization of a novel endogenous murine parkin mutationJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Chenere P. Ramsey J. Neurochem. (2010) 113, 402,417. Abstract Various mutations in the PARK2 gene which encodes the protein, parkin, are causal of a disease entity-termed autosomal recessive juvenile parkinsonism. Parkin can function as an E3 ubiquitin-protein ligase, mediating the ubiquitination of specific targeted proteins and resulting in proteasomal degradation. Parkin is thought to lead to parkinsonism as a consequence of a loss in its function. In this study, immunoblot analyses of brain extracts from Balb/c, C57BL/6, C3H, and 129S mouse strains demonstrated significant variations in immunoreactivity with anti-parkin monoclonal antibodies (PRK8, PRK28, and PRK109). This resulted partly from differences in the steady-state levels of parkin protein across mouse strains. There was also a complete loss of immunoreactivity for PRK8 and PRK28 antibodies in C3H mice due to was because of a homologous nucleotide mutation resulting in an E398Q amino acid substitution. In cultured cells, parkin harboring this mutation had a greater tendency to aggregate, exhibited reduced interaction with the E2 ubiquitin-conjugating enzymes, UbcH7 and UbcH8, and demonstrated loss-of-function in promoting the proteosomal degradation of a specific putative substrate, synphilin-1. In situ, C3H mice displayed age-dependent increased levels of brain cortical synphilin-1 compared with C57BL/6, suggesting that E398Q parkin in these mice is functionally impaired and that C3H mice may be a suitable model of parkin loss-of-function similar to patients with missense mutations. [source] CYP1A2 polymorphism (C,>,A at position ,163) in Ovambos, Koreans and MongoliansCELL BIOCHEMISTRY AND FUNCTION, Issue 5 2007Junko Fujihara Abstract Cytochrome P450 1A2 (CYP1A2) plays an important role in metabolizing drugs and xenobiotics, and is a possible participant in the development of several human diseases. Recent studies have shown that genetic polymorphism of ,163 C,>,A single nucleotide mutation of CYP1A2 increases the risk of myocardial infarction and modulates CYP1A2 activity. In this study, we investigated the frequency of the ,163 C,>,A mutation in Ovambos (n,=,177), Koreans (n,=,250) and Mongolians (n,=,153) and compared our results with other studies. Detection of this single nucleotide polymorphism was by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The frequencies of mutation (CYP1A2*,163A) in the Ovambos, Koreans and Mongolians were 0.46, 0.32 and 0.21, respectively. Ovambos showed a relatively higher frequency of mutation, similar to that of Tanzanians, while the Mongolians showed the lowest frequency of all study groups, including those from previous studies. This study is the first to investigate the distribution of the CYP1A2 (,163 C,>,A single nucleotide polymorphism) mutant allele in Ovambo, Korean and Mongolian populations. Copyright © 2006 John Wiley & Sons, Ltd. [source] Two novel somatic mutations in the human interleukin 6 promoter region in a patient with sporadic breast cancerINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 6 2003A. Saha Summary Two new single nucleotide mutations were observed within the promoter region of human interleukin-6 gene (IL-6) in the tumour sample of a patient with sporadic breast cancer, which was a somatic change. Both mutations, one at ,125 (C > G) and the other at position ,173 (G > T) from the translation start site, were transversions observed at new positions, not reported earlier. In addition to these two novel mutations in this patient, a known somatic polymorphism was also observed at position ,174 (G > C) (from the transcription initiation site, redesignated as ,236 from the translational initiation site as per the HUGO nomenclature). Further, a preliminary comparative analysis of the studied promoter region by the ,ConsInspector 3.0' program, where the mutated sequence (AF362378) was compared with the sequence existing in the database (Y00081), depicted the presence of the variations in putative binding sites for transcription factors such as glucocorticoid response element (GRE) and nuclear factor kappa-B (NF,-B), which could lead to differential expression of this gene. [source] Novel variants within the coding regions of the Slc11A1 gene identified in Bos taurus and Bos indicus breedsJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 1 2008R. Martínez Summary Although in the cow the genetic resistance to brucellosis has been previously attributed to the Slc11A1 gene encoding Nramp1 protein, none of the mutations described to date seems to be the cause. To be able to associate another polymorphism of the gene to brucellosis resistance, we characterized the gene and identified in different breeds of Bos taurus and Bos indicus, six new variants among a total of 11 single nucleotide mutations, of which five occurred in the coding sequence (three are missense mutations), one in the promoter region and five in introns. The allelic and genotypic frequencies calculated revealed differences (p < 0.05) among the breeds studied. [source] Mitochondrial DNA mutations as a fundamental mechanism in physiological declines associated with agingAGING CELL, Issue 1 2003Jeong W. Pak Summary The hypothesis that mitochondrial DNA damage accumulates and contributes to aging was proposed decades ago. Only recently have technological advancements, which facilitate microanalysis of single cells or portions of cells, revealed that mtDNA deletion mutations and, perhaps, single nucleotide mutations accumulate to physiologically relevant levels in the tissues of various species with age. Although a link between single nucleotide mutations and physiological consequences in aging tissue has not been established, the accumulation of deletion mutations in skeletal muscle fibres has been associated with sarcopenia. Different, and apparently random, deletion mutations are specific to individual fibres. However, the mtDNA deletion mutation within a phenotypically abnormal region of a fibre is the same, suggesting a selection, amplification and clonal expansion of the initial deletion mutation. mtDNA deletion mutations within a muscle fibre are associated with specific electron transport system abnormalities, muscle fibre atrophy and fibre breakage. These data point to a causal relationship between mitochondrial DNA mutations and the age-related loss of muscle mass. [source] NS5A mutations predict biochemical but not virological response to interferon-, treatment of sporadic hepatitis C virus infection in European patientsJOURNAL OF VIRAL HEPATITIS, Issue 4 2001I. Stratidaki The NS5A region of the hepatitis C virus (HCV) genome has been reported by Japanese but not European investigators to be a significant factor in predicting interferon (IFN) response patients with HCV of genotype 1. We correlated the NS5A region with treatment outcome in patients with sporadic HCV infection. Twenty-eight patients (10 men, 18 women, mean age 60 ± 2 years) with histologically proven HCV chronic hepatitis, genotype 1b, were treated with 6 MU IFN-, for 6 months. The 6954,7073 area of the NS5A region was directly sequenced for nucleotide and amino acids mutations and the results were related to biochemical and virological response. None of the patients had a strain with nucleotide sequence identical to the Japanese HCV-J. However, in five strains the nucleotide mutations led to synonymous amino acids and the amino acid sequences were identical to the prototype Japanese strain. Only 2/28 patients had four or more amino acid mutations (mutant strains) while 21 demonstrated an intermediate type and five belonged to the wild-type. The most frequent non-synonymous substitution was at position 6982 (A,G) corresponding to an amino acid change at codon 2218 (His,Arg). All patients with the wild-type were biochemical nonresponders while the two patients with the mutant strains had a sustained biochemical response. Twenty-three percent of the intermediate type had a sustained biochemical response. NS5A mutations predict the biochemical but not the virological response of patients. Virological response was poor and unrelated to the type of HCV strain. Biochemical responders had significantly lower amino acid mutations (1.14 ± 0.19) compared with nonresponders (2.57 ± 1.4, P < 0.003) as well as lower aminotransferase values (P < 0.01). Hence, mutational analysis of the NS5A region showed that our patients have a mutational profile similar to the European studies with a wild-type that is slightly different from the Japanese HCV-J sequence. The biochemical, but not the virological response to IFN-, is similar to the Japanese studies, with no response of the patients with wild-type sequence, a good response in the limited number of patients with mutant strains and 23% response rate in the patients with intermediate type sequences. [source] Parallel analysis of mutant human glucose 6-phosphate dehydrogenase in yeast using PCR colonies,BIOTECHNOLOGY & BIOENGINEERING, Issue 5 2005Joshua Merritt Abstract We demonstrate a highly parallel strategy to analyze the impact of single nucleotide mutations on protein function. Using our method, it is possible to screen a population and quickly identify a subset of functionally interesting mutants. Our method utilizes a combination of yeast functional complementation, growth competition of mutant pools, and polymerase colonies. A defined mutant human glucose-6-phosphate-dehydrogenase library was constructed which contains all possible single nucleotide missense mutations in the eight-residue glucose-6-phosphate binding peptide of the enzyme. Mutant human enzymes were expressed in a zwf1 (gene encoding yeast homologue) deletion strain of Saccharomyces cerevisiae. Growth rates of the 54 mutant strains arising from this library were measured in parallel in conditions selective for active hG6PD. Several residues were identified which tolerated no mutations (Asp200, His201 and Lys205) and two (Ile199 and Leu203) tolerated several substitutions. Arg198, Tyr202, and Gly204 tolerated only 1-2 specific substitutions. Generalizing from the positions of tolerated and non-tolerated amino acid substitutions, hypotheses were generated about the functional role of specific residues, which could, potentially, be tested using higher resolution/lower throughput methods. © 2005 Wiley Periodicals, Inc. [source] | |||||||||||||