It is clear that many effects of mutations on behavior of collagen molecules need to be taken into account when determining how they result in lethal mutations.
This disparate behavior does not bode well for molecular-evolutionary calculations that assume 4×4 mutation and "neutral" behavior of SC mutations, and it bodes even worse for calculations assuming that 4×4 mutation rates are the same in constrained and unconstrained DNA of the same or dissimilar GC content (see also Discussion).
The effect of the p.T59R mutation on the behavior of Trisk 32 was first studied by expression in the non-muscle COS-7 cell line, and analysis of the localization of the wild-type (WT) (T32) or mutant protein T32-T59RR) by confocal microscopy.
A typical comparison between the reconstructed and observed mutation profile is given in Figure S2 B. The concordance indicated that five signatures were sufficient to describe the general behavior of mutation profiles of the 21 breast cancer samples.
The concordance indicated that five signatures were sufficient to describe the general behavior of mutation profiles of the 21 breast cancer samples.
Moreover, our study confirms the observation that the rosR mutation significantly affects the behavior of bacterial cells, as evidenced by their altered morphology, flagellation, motility, and aggregation ability.
In summary, our results show that topology of mutations predicts in part the behavior of mutant CBS, and that misfolding may be an important and frequent pathogenic mechanism in CBS deficiency.
In another aspect, although there have been achievements in engineering POx for better thermostability and catalytic efficiency (Bastian et al. 2005; Heckmann-Pohl et al. 2006; Masuda-Nishimura et al. 1999), it is not known how the mutations would affect the behavior of the pyranose oxidase in breadmaking.
Although the biological relevance of this dominant-negative behavior is currently not clear, this effect provides another interesting assay to further investigate the behavior of mutations in the TI domain.
Reintroducing the APPA673T mutation into rodent will provide an interesting animal model to further investigate the neuronal behavior of this mutation.
