The experiment and subsequent dissection of mutations was not perfect, which led to our investigation of the impact of the overall significance level on assigning mutants into mutational groups and subsequent inference.
In this case, several mutations were introduced that led to six additional negative charges.
Three of the mutations are predicted to lead to truncated PNPLA2/ATGL proteins with intact patatin domains, and the fourth leads to a single amino acid substitution (P195L).
We screened for mutations in the whole exonic regions of Sl-eIF4E1, and focalized the screening for other genes only on regions where natural mutations were shown to lead to virus resistance i.e., exons 1 to 3 for Sl-eIF iso 4E, Sl-eIF iso 4E-exonE2 and MiF4G, MA3 and eIF4E-binding domains for Sl-eIF4G genes (Figure 1).
Overall, most mutations were predicted to lead to a truncated or absent protein.
In all, 11 of the mutations are predicted to lead to a truncated protein (four nonsense mutations, four frameshift deletions, one frameshift insertion and two splice site mutations).
The vast majority of the mutations are predicted to lead to a premature stop codon (39 frameshifts, 15 nonsense mutations and 24 splice site disruptions).
Thus, MED12 mutations are likely to lead to specific functional effects not concurrently replicated by mutations in other components of the Mediator kinase module.
These mutations were shown to lead to increased TERT expression, most likely by creating ETS transcription-factor-binding sites (Horn et al, 2013; Huang et al, 2013).
Taken together, the vast majority of NEB mutations are predicted to lead to a degradation and or denaturation of many nebulin isoforms.
