We considered the possibility that the 0ΔNLS mutation might reduce the spread of HSV-2 0ΔNLS infection.
Page 5 introduces the amorphic and hypomorphic classes of mutation, and asks how a mutation might "reduce but not eliminate or change the activity of a gene product".
As conformational changes in the DNA RepD complex are essential for nicking, it is possible that mutation of N189 might reduce bending activity.
However, this approach would miss the tumour-associated mutations occurring outside the mutation hot spots and, hence, might reduce the sensitivity of the test.
Alternatively, a special chromatin structure of imprinted genes might reduce overall mutation rates in the germ lines, thereby leading to the observed lower synonymous substitution rates.
Currently, it is unknown whether biomarker status changes after exposure to chemotherapy or on progression, but a recent study by Bai et al. demonstrates that chemotherapy might reduce EGFR mutation frequency in both plasma and biopsy samples [ 5].
Further, most testing of NAI sensitivity currently occurs with the NI assay, which would miss NAI-resistance due to HA mutations, and limited prescription of zanamivir might reduce the chance of observing clinical zanamivir resistance.
Mutations may impair Parkin activity, which might reduce the clearance and aggregation of proteins.
Escape mutations might confer reduced viral fitness by coincidentally increasing epitope processing (Tenzer et al., 2009) and/or reducing viral replication or infectivity (Goulder and Walker, 2012).
In other words, the DSE mutation in the Nnd1-dse allele might reduce the activity of this negative regulator more than it affects the function of CstF, resulting in a net increase in N mRNA 3' processing that in turn increases N mRNA polyadenylation and translation, Nintra production, and Notch signaling.
