As used herein, an "allele" or "allelic sequence" is an alternative form of the gene which may result from at least one mutation in the nucleic acid sequence. Alleles may result in altered mRNAs or polypeptides whose structure or function may or may not be altered. Any given gene may ...
The potential impact of CFTR modulator therapies on glucose balance depends on the CF causing mutation, and thus, the type of CFTR modulator and their possible association. Small pilot studies from a few years ago pointed out the improvement of glycaemic control with IVA [53,54]. In addition,...
Haldane JBS (1935) The rate of spontaneous mutation of a human gene. J Genet 83(3):235–244 Google Scholar Hanifin CT, Brodie Jr ED, Brodie III ED (2008) Phenotypic mismatches reveal escape from arms-race coevolution. PLOS Biol 6(3):471–482 CAS Google Scholar Hanifin CT, Yotsu-...
A specific mutation in one of the variants has been shown to display a different phenotype in relation to a human heart disease than other variants and known human sodium channel subunits with corresponding mutations. The present invention provides new tools to study mutations and to design or ...
317 The use of rectal biopsies318 or intestinal organoids319,320 from CF patients allows a mutation-specific assessment of drug effectiveness in achieving these goals. CFTR internalization is enhanced by the WNK (with no lysine kinase)/SPAK signaling pathway and counteracted by IRBIT/PP1.321–...
Complete loss of the cytoplasmic carboxyl terminus of the KCNQ2 potassium channel: a novel mutation in a large Czech pedigree with benign familial neonatal convulsions or other epileptic phenotypes. Epilepsia 2004;45: 384–390. CAS PubMed Google Scholar Tang B, Li H, Xia K, et al. A ...
A human Piezo1 GOF mutation in brain ECs impairs hyperemic responses Introducing a GOF mutant Piezo1 channel in ECs throughout the vasculature (i.e., pan-endothelial) impaired FH (Figs. 2, 3). It is possible that altered peripheral vascular Piezo1 function in GOF mice contributes to the ob...
2e). To our surprise, W54A single mutation is sufficient to revive the channel activity of CeOTOP8 (Fig. 2f), indicating that the Trp54-mediated dimerization interaction plays the key role in channel inhibition. As further discussed in the following study of mouse OTOP2, the C-barrel of ...
A-803467 (1) has been described as a 100- to 1000-fold pharmacologically selective Nav1.8 state-dependent blocker displaying analgesia in a variety of pain models. However, clinical development has been hampered by poor bioavailability[16,17]. Mutation studies suggest a binding site that partially...
After crossover and mutation, a new population is generated by combining the parents, and the selection mechanism is also identified. Finally, the iteration is completed to generate the Pareto optimal front. Figure 7. The flow chart of the NSGA-II method. In the optimization of geometric ...