For clade 1.1, the virus that had the R430W mutation showed reduced inhibition by oseltamivir, zanamivir, and laninamivir; in clade 2.3.2.1, the virus that had the H275Y mutation showed highly reduced inhibition by oseltamivir and peramivir.
However, despite this apparent random evolution, we identified several cooccurring mutations (Circos plots in Figure 5) that showed highly connected mutation patterns between these three viral populations.
Skin, lung, and urinary bladder showed highly independent mutation spectra (maximum discordance value = 1.48 for skin versus brain), in agreement with the presence of specific factors responsible for a large number of the respective tumors (UV light, smoking, aromatic amines).
The CCB256 primer showed highly conserved sequences and minute single polymorphic nucleotides with no deletion or mutation.
Dogs homozygous for the nt230[del4] MDR1 mutation show highly increased susceptibility to many drugs commonly used in veterinary medicine including ivermectin.
A series of highly conserved flanking cysteines (Cys-53, Cys-77, and Cys-83) were mutated to alanine, but none of these mutations showed any effect on either enzyme activity.
Sequence alignment for novel missense mutations showed Ala314, Gly386, Tyr470, Arg85 and Arg445 amino acid residues to be highly conserved throughout mammalian species.
The yMLH1-G64R mutant protein confers an intermediate phenotype, but nevertheless shows highly elevated mutation rates.
Secondary mutations show clonal evolution, and newly acquired mutations are highly heterogeneous with regard to the metastatic sites in a patient, and sometimes even within a particular tumor nodule, although the primary mutation is the same throughout all lesions.
Those without the mutation showed the usual signs of deprivation.
