In conclusion, we describe a child with two functionally opposing MC2R mutations.
The inability of the Y129C mutant receptor to localise to the cell surface in this child essentially inactivates the ability of the F278C mutation to cause constitutive activity and a Cushing's syndrome phenotype, thus providing a unique molecular explanation for the existence of two opposing MC2R mutations resulting in FGD.
Unlike the Ames and TK assays, the comet assay directly tests for DNA damage, as opposed to mutations that arise as a result of damage, offering an important advantage.
Since drug resistance mutations are subject to evolutionary pressure caused by the drug treatment they should be independent of geographic location and therefore be more widely distributed over the tree, as opposed to mutations driven by other environmental factors which tend to rather concentrate in small subtrees.
The C3H/HeJ F9−/− model shows a F9 genotype dependency of inhibitor formation and anaphylaxis that closely mirrors the experience for treatment of human subjects with severe haemophilia B, who are at elevated risk with gene deletions as opposed to mutations that retain endogenous coding information (Verma et al, 2010).
Missense mutations, as opposed to truncating mutations, are often conservatively interpreted as variants of unknown significance until proven otherwise.
In particular, there is still a controversy about the proportion of deleterious or slightly deleterious mutations as opposed to advantageous mutations resulting from M A experiments [ 28, 29].
As opposed to mutation 531 which is the most commonly observed mutation in rifampicin-resistant isolates in many parts of the world, e.g., in Brazil (54%) [ 56], the USA (35%) [ 57], India (38.7%) [ 58], Germany (65%) [ 59] and Australia (52%) [ 60].
The MS theory of causal forces urges us to choose between the opposing pressures of mutation and selection.
