Search results for "Dynamic mutation"
showing 3 items of 3 documents
Phenotype Correlation and Intergenerational Dynamics of the Friedreich Ataxia GAA Trinucleotide Repeat
1997
Summary The Friedreich ataxia (FA) mutation has recently been identified as an unstable trinucleotide GAA repeat present 7–22 times in the normal population but amplified as many as > 1, 000 times in FA. Since it is an autosomal recessive disease, FA does not show typical features observed in other dynamic mutation disorders, such as genetic anticipation. We have analyzed the GAA repeat in 104 FA patients and 163 carrier relatives previously defined by linkage analysis. The GAA expansion was detected in all patients, most (94%) of them being ho-mozygous for the mutation. We have demonstrated that clinical variability in FA is related to the size of the expanded alleles: milder forms of the …
Genome-Wide Estimation of the Spontaneous Mutation Rate of Human Adenovirus 5 by High-Fidelity Deep Sequencing
2016
Rates of spontaneous mutation determine the ability of viruses to evolve, infect new hosts, evade immunity and undergo drug resistance. Contrarily to RNA viruses, few mutation rate estimates have been obtained for DNA viruses, because their high replication fidelity implies that new mutations typically fall below the detection limits of Sanger and standard next-generation sequencing. Here, we have used a recently developed high-fidelity deep sequencing technique (Duplex Sequencing) to score spontaneous mutations in human adenovirus 5 under conditions of minimal selection. Based on >200 single-base spontaneous mutations detected throughout the entire viral genome, we infer an average mutatio…
Mechanisms of viral mutation
2016
The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than double-strand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be intro…