Search results for "MUTATION"
showing 10 items of 2830 documents
Biomedical implications of viral mutation and evolution
2012
Mutation rates vary hugely across viruses and strongly determine their evolution. In addition, viral mutation and evolution are biomedically relevant because they can determine pathogenesis, vaccine efficacy and antiviral resistance. We review experimental methods for estimating viral mutation rates and how these estimates vary across viral groups, paying special attention to the more general trends. Recent advances positing a direct association between viral mutation rates and virulence, or the use of high-fidelity variants as attenuated vaccines, are also discussed. Finally, we review the implications of viral mutation and evolution for the design of rational antiviral therapies and for e…
Evaluating the effect of spastin splice mutations by quantitative allele-specific expression assay
2010
Background: Mutations in the SPG4/SPAST gene are the most common cause for hereditary spastic paraplegia (HSP). The splice-site mutations make a significant contribution to HSP and account for 17.4% of all types of mutations and 30.8% of point mutations in the SPAST gene. However, only few studies with limited molecular approach were conducted to investigate and decipher the role of SPAST splice-site mutations in HSP. Methods: A reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and quantitative allele-specific expression assay were performed. Results: We have characterized the consequence of two novel splice-site mutations (c.1493 + 1G>A and c.1414−1G>A) in the SPAST gene…
Simulating the Influence of Conjugative Plasmids Kinetic Values on the Multilevel Dynamics of Antimicrobial Resistance in a Membrane Computing Model
2020
AbstractPlasmids harboring antibiotic resistance genes differ in their kinetic values as plasmid conjugation rate, segregation rate by incompatibility with related plasmids, rate of stochastic loss during replication, cost reducing the host-cell fitness, and frequency of compensatory mutations to reduce plasmid cost, depending on the cell mutation frequency. How variation in these values influence the success of a plasmid and their resistance genes in complex ecosystems, as the microbiota? Genes are located in plasmids, plasmids in cells, cells in populations. These populations are embedded in ensembles of species in different human hosts, are able to exchange between them bacterial ensembl…
Identification of two new mutations in TRPS 1 gene leading to the tricho-rhino-phalangeal syndrome type I and III.
2009
Confirmation of EP300 gene mutations as a rare cause of Rubinstein-Taybi syndrome.
2007
The Rubinstein-Taybi syndrome (RSTS, MIM 180849), a dominant Mendelian disorder with typical face, short stature, skeletal abnormalities, and mental retardation, is usually caused by heterozygous mutations of the CREBBP gene, but recently, EP300 gene mutations were reported in three individuals. Using quantitative PCR (for the CREBBP and EP300 genes) and genomic sequencing (for the EP300 gene), we studied here 13 patients who had shown no mutation after genomic sequencing of the CREBBP gene in a previous investigation. Two new disease-causing mutations were identified, including a partial deletion of CREBBP and a 1-bp deletion in EP300, c.7100delC (p.P2366fsX2401). The 1-bp deletion represe…
Fixation of mutations at the VP1 gene of foot-and-mouth disease virus. Can quasispecies define a transient molecular clock?
1991
The number of nucleotide (nt) substitutions found in the VP1 gene (encoding viral capsid protein) between any two of 16 closely related isolates of foot-and-mouth disease virus (FMDV) has been quantified as a function of the time interval between isolations [Villaverde et al.,J. Mol. Biol. 204(1988)771-776]. One of them (isolate C-S12) includes some replacements found in isolates that preceded it and other replacements found in later isolates. The study has revealed alternating periods of rapid evolution and of relative genetic stability of VP1. During a defined period of acute disease, the rate of fixation of replacements at the VP1 coding segment was 6 × 10-3 substitutions per nt per year…
Application of DNA Polymorphisms in Paternity Testing in Germany: Solution of an Incest Case Using Bacteriophage M13 Hybridization with Hypervariable…
1988
More than 25 blood, serum, and enzyme polymorphisms have been introduced into paternity testing in Germany in recent years (Rittner, 1975). If a “no” decision is defined by exclusion, and a “yes” decision requires a probability of 99.73 % or more, more than 90 % of court cases can be solved in this respect. A few cases not being clarified by a standard expertise include: 1) Cases with more than one alleged man if the men and/or the mother and the men are related. 2) Some cases where the putative father is deceased, and neither the parents nor the legitimate offspring are available for the study. 3) Cases where possible exclusion in a given polymorphic system interferes with an overall evide…
Screening for multiple hereditary hypercoagulability factors using the amplification refractory mutation system
2003
Many hereditary factors have been implicated in the development of arterial and/or venous thromboembolic diseases. A number of these risk factors can be identified by the amplification refractory mutation system (ARMS). However, the underlying technical conditions for performing ARMS are highly variable, and depend on which risk factors are being analyzed. We have now developed a novel ARMS-based system to simultaneously screen for multiple hypercoagulability factors under identical PCR conditions. This can greatly simplify the process of screening for hereditary hypercoagulability.
Expanding the phenotype of ASXL3 ‐related syndrome: A comprehensive description of 45 unpublished individuals with inherited and de novo pathogenic v…
2021
The study aimed at widening the clinical and genetic spectrum of ASXL3-related syndrome, a neurodevelopmental disorder, caused by truncating variants in the ASXL3 gene. In this international collaborative study, we have undertaken a detailed clinical and molecular analysis of 45 previously unpublished individuals with ASXL3-related syndrome, as well as a review of all previously published individuals. We have reviewed the rather limited functional characterization of pathogenic variants in ASXL3 and discuss current understanding of the consequences of the different ASXL3 variants. In this comprehensive analysis of ASXL3-related syndrome, we define its natural history and clinical evolution …