We next evaluated the consequences of mutations of AnkG characterized in Figure 3 on its function in clustering Nav channels and Nfasc at the AIS in cultured hippocampal neurons.
It indicates that the amount of normal protein is decreased (as seen in inborn errors of metabolism) Gain of function It refers to the functional consequences of mutations on protein function.
Although the mechanistic consequences of mutations on splice sites are fairly easy to interpret, evaluating precisely how inherited disease-causing mutations influence the loss or gain of ESE/ESS motifs remains challenging [ 18].
Algorithms to evaluate the structural and functional consequences of mutations on proteins (e.g. PolyPhen and SIFT) are commonly used to assess the potential deleterious effects of mutations [ 25- 27].
We organize this presentation into five main categories, denoting the kinds of problems being addressed by the various studies: identifying dysregulated pathways, elucidating consequences of mutations on network activities, integrating network operation into cell behavioral functions, integrating cell behavior into tissue-level processes and predicting effects of molecular interventions.
Michaud et al. used conditionally immortalized mouse podocytes infected with adenoviral constructs containing WT or K256E murine Actn4 to assess the functional consequence of mutations on subcellular localization, adhesion, spreading, migration, and formation of foot process-like peripheral projections [ 65].
Our understanding of the evolutionary consequences of mutation relies heavily on estimates of the rate and fitness effect of spontaneous mutations generated by mutation accumulation (MA) experiments.
The consequences of mutations depend on the environment.
Prediction of the functional consequences of mutations based on long-term evolutionary conservation has been described in the context of human genetic studies [ 31- 33] but there is even greater scope for this approach to assist studies in P. falciparum, where the contribution of non-adaptive change appears to be log-orders of magnitude higher.
Consequences of the mutation on gene function are included in the Mutation Databases as far as their relevance to the disease mechanism is demonstrated.
