Small-effect mutations require more underlying genetic variation to produce a clone with the same fitness as a large-effect mutation.
Although pipelines to analyze next-generation sequencing (NGS) data have become commonplace, the systematic analysis of mutations requires more time and effort than is available in routine hospital practice.
All cell lines displayed a very weak sensitivity with IC50 values higher than 5 μ M. By contrast, in V600E-mutated melanoma cells, IC50 values were lower than 100 n M, whereas V600E unmutated cells (including cells carrying other BRAF mutations) required more than 1 μ M to display any sensitivity.
Hence, the overall direction of epistasis for fitness, and the possible role of compensatory mutations in pushing toward net antagonistic epistasis among random mutations, will require more study in higher organisms.
Complex multifactorial diseases, which may depend on human-specific variants with small effect size or more specific molecular effects such as gain-of-function mutations, will require more customized approaches such as knockin of specific human mutations.
6 The studies for the new fluoroquinolone, moxifloxacin, have demonstrated that mutations in the target genes require more than one mutation.
Increases in expression could be achieved by a diverse array of mutations in the repressor or the operator that lower the binding affinity, whereas decreases in expression would require more rare mutations that increase affinity or mutations in the lacZ promoter.
These phenotypic mutations might underlie evolution of complex traits that require more than one mutation (a simplest example of a potentially beneficial structural feature of proteins that requires two mutations is a new disulfide bond).
But now, he added, it is becoming increasingly clear that cancers require more than mutations to progress.
The cohort study found evidence supporting the "female protective model", a theory that suggests that females require more extreme genetic mutations than males before they develop certain sorts of disorders.
