They found that these passaged strains showed additional attenuation in rats and that this phenotypic change was associated with changes in quasispecies heterogeneity rather than fixation of any individual mutation.
Alexey Kondrashov's deterministic mutation hypothesis (DMH) assumes that each organism has more than one harmful mutation and the combined effects of these mutations are more harmful than the sum of the harm done by each individual mutation.
Cooperativity between protein subunits is evidenced by a disproportionate effect in the presence of multiple substitutions than predicted by an analysis of each individual mutation.
The sensitivity of OncoMap is influenced by inherent technological parameters, individual mutation assay performance characteristics, and the quality and purity of tumor tissue.
Primers were designed to detect each individual mutation, using each respective reference sequence and Vector NTI (Supplemental Tables S1 and S2).
Our results indicated that individual mutation in either APP or PS1 alone is insufficient to trigger overtly compromised cardiomyocyte contractile function compared with concurrent presence of both.
Among the EBS analyzed, the individual mutation of EBS3 or of EBS5 markedly affected the activity of the reporter in endothelial and in fibroblast cells, but with a greater effect with EBS5.
Though individual mutation has a low frequency, their gene-wise or pathway-wise aggregate frequency could be substantially large, which makes it possible for rare variants to be the cause of common diseases.
Individual mutation to alanine of residues Phe692, Glu693, Asn694, Leu696, His697, Asn698 and Ile700 resulted in a 10- to 30-fold loss in ligand binding, whilst mutation of Phe701 resulted in no detectable ligand binding.
To examine if individual mutation in APP or PS1 is capable of eliciting myocardial contractile dysfunction independently, cardiomyocyte mechanical function was assessed in the gender- and weight-matched mice with mutation of APP or PS1 (3 mice each, body weight = 27 29 g), or both (APP/PS1).
This revealed that individual mutation of all of these residues abolished binding to the peptide.
