If the mutation is truly recessive, the other three quarters will be perfectly viable, and two out of three among that viable offspring will be heterozygous for the mutation.
Whereas the genetic changes are interesting, some somatic mutations are truly remarkable because of the striking phenotypic changes that result.
From these data alone, it is unclear which of the mutations is truly beneficial, and if the selective benefit of the second mutation is due to amelioration of the pleiotropic costs of the first [ 31].
As long as one does not recognise that many mutations are truly recessive, one simply cannot venture towards the idea that deleterious ones are driving the absolute requirement for inbreeding, and advantageous ones the initial steps of speciation.
Regardless of whether another autistic phenotype associated with MECP2 mutations is truly autism, it is likely that the phenotypic differences from RTT or XLMR arise from differences in genetic background and environmental exposures in each affected individual.
This measure is less sensitive than overall mutation frequency since some mutations detected more than once may be the result of independent events rather than clonal outgrowth, but using this end point assures that the observed unique mutations are truly derived from independent events.
While the absence of inactivating MH2 germline mutations from this study provides compelling evidence that SMAD3 and SMAD4 mutations are truly rare in breast cancer, this study cannot comprehensively exclude the presence of other mutations since the Mad-Homology 1 (MH1) and the variable linker region were not screened.
The establishment of databases of LoF variants, together with careful evaluations of the known functional evidence in the context of the phenotypes of interest, will be required to determine if a gene with LoF mutations is truly causal, at least within particular genetic backgrounds.
As a result, we suggest that cryptic variation in the mutation rate is truly cryptic, in the sense that the mutation rate does not appear to depend on any specific primary sequence context.
As difficult as my health problems themselves are, it was the lack of hope brought on by seeing my genetic mutation in black and white that was truly devastating.
