Search results for "Transversion"

Activating mutations in human c-Ha-ras-1 protooncogene induced by stereoisomeric fjord-region benzo[c]chrysene diol-epoxides.

1995

The mutagenicity of fjord-region benzo[c]chrysene diol-epoxide (BcCDE) stereoisomers((+) anti-BcCDE, (-)anti-BcCDE, (+)syn-BcCDE, and (-)syn-BcCDE) was studied in a forward-mutation system. pEC plasmid containing the human c-Ha-ras-1 proto-oncogene was reacted in vitro with each optically active isomer separately and transfected into NIH/3T3 cells. Morphologically transformed foci were cloned, and DNA obtained from these foci was tested for the presence of Ha-ras-1 sequence by Southern blot analysis. A total of 50 transformed foci (11-14 for each diastereomer) were generated. To determine the nature of mutations responsible for activating the proto-oncogene, regions of the gene likely to co…

Identification of two novel polymorphisms and a rare deletion variant in the human dopamine D4 receptor gene

1995

We report two novel polymorphisms and a rare deletion variant in the human dopaine D4 receptor gene. The two polymorphisms are characterized by single base pair substitutions, namely a G-->C transversion changing codon 11 from GGG (encoding Gly) to CGG (encoding Arg) and a C-->T transition in position -11 upstream from the start codon. The Arg11 variant occurs at a frequency of about 1% and the C-->T transition at a frequency of about 7% in German control subjects (n = 148). Allele frequencies observed in patients suffering from schizophrenia (n = 256) and bipolar affective disorder (n = 99) were similar. The deletion variant is characterized by a 21 bp deletion affecting codons 36 to 42 co…

Highly heterogeneous mutation rates in the hepatitis C virus genome.

2016

Spontaneous mutations are the ultimate source of genetic variation and have a prominent role in evolution. RNA viruses such as hepatitis C virus (HCV) have extremely high mutation rates, but these rates have been inferred from a minute fraction of genome sites, limiting our view of how RNA viruses create diversity. Here, by applying high-fidelity ultradeep sequencing to a modified replicon system, we scored >15,000 spontaneous mutations, encompassing more than 90% of the HCV genome. This revealed >1,000-fold differences in mutability across genome sites, with extreme variations even between adjacent nucleotides. We identify base composition, the presence of high- and low-mutation clusters a…

HCV-1b intra-subtype variability: Impact on genetic barrier to protease inhibitors

2013

Abstract Due to error-prone RNA polymerase and the lack of proofreading mechanisms, to the spread worldwide and probable long-term presence in human population, HCV showed a high degree of inter- and intra-subtype genetic variability. Protease inhibitors (PIs), a new class of drugs, have been designed specifically on the HCV genotype 1 NS3 protease three-dimensional structure. The viral genetic barrier limits the efficacy of PIs, and fourteen loci in the HCV NS3 gene are involved in resistance to PIs. A sensitive method (15 UI/ml) for study the HCV genetic profile of 125 strains from patients naive to PIs, was developed through the use of new degenerate primers for subtype 1b. We observed t…

A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population.

2002

Myoadenylate deaminase deficiency is the most common metabolic disorder of skeletal muscle in the Caucasian population, affecting approximately 2% of all individuals. Although most deficient subjects are asymptomatic, some suffer from exercise-induced myalgia suggesting a causal relationship between a lack of enzyme activity and muscle function. In addition, carriers of this derangement in purine nucleotide catabolism may have an adaptive advantage related to clinical outcome in heart disease. The molecular basis of myoadenylate deaminase deficiency in Caucasians has been attributed to a single mutant allele characterized by double C to T transitions at nucleotides +34 and +143 in mRNA enco…

Sequence analysis of the DRB1 promoter reveals limited polymorphism with no influence on gene expression.

2001

HLA-class II promoters contain a set of conserved regulatory regions necessary for constitutive and induced gene expression. For the HLA-DQB as well as for the DRB1 promoter sequence, polymorphisms with influence on gene expression have been reported. In contrast to these data we could show that there is very limited allele-specific polymorphism among the HLA-DRB1 promoter alleles. In a long range PCR we amplified a DNA sequence containing the promoter and the second exon of the DRB1 gene in one fragment. Nested PCR products of this PCR fragment for the promoter and for the second exon were analysed by DNA sequencing to allow the linkage of a promoter to its DR allele. Most investigated DRB…

Correspondence to Sand et al. “Critical Reappraisal of a Catechol-O-Methyltransferase Transversion Variant in Schizophrenia”

2010

Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia

1996

Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT{sub 1F}) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T{r_arrow}A transversion in the third position of codon 261 (encoding isoleucine), a silent C{r_arrow}T transition in the third position of codon 176 (encoding histidine), and a C{r_arrow}T transition in position -78 upstream from the start codon. The lack of significan…