Possible sources of bias include sequence errors, presence of specific sequence mutations associated with certain malignancies, unequal presentation of different physiological or pathological libraries and the expression of splice variants in certain malignancies.
The replication introduces mutations with a certain probability.
It is possible that the S134N mutation, along with certain others that do not appear to destabilize SOD1 (e.g. D101N [59]), cause ALS by a mechanism that does not involve amyloid formation or other forms of aggregation.
However, these mutations might not be detected with certain mutation-specific detection methods (Anderson et al, 2012) and consequently these patients might be excluded from clinical trials with BRAF inhibitors or regular treatment with vemurafenib (Flaherty et al, 2010).
The fitness dynamics along a lineage resemble a random walk on which each step corresponds to a mutation with a certain effect on fitness.
However, this type of mutation might not be detected with certain mutation-specific assays [ 7, 33]; consequently, affected patients might be excluded from clinical trials with BRAF inhibitors or regular treatment with vemurafenib [ 16].
Therefore, different types of mutations might lead to different defects, such as ASDs with certain mutations and cardiomyopathy or skeletal myopathies with other mutations.
The H486R mutation is associated with certain types of glaucomas [37], [38].
These concerns were further reinforced by reports of an increased frequency of malignancies observed in patients receiving vicriviroc [11,12], another investigational CCR5 antagonist, and by reports of deleterious outcomes in patients with the CCR5 delta 32 mutation following infections with certain viruses, including West Nile and yellow fever [22 24].
