Compensatory mutations that maintained secondary structure were located manually and the VARNA software package [ 93] was used to illustrate RNA secondary structure.
The BIC database was used as resource for a range of mutation types analyzed, including missense (n = 17), nonsense (n = 167), splicing (n = 5), insertion or deletion mutations that maintained the ORF (n = 19), unclassified variant (UV; n = 387) and polymorphisms (n = 12).
Since Aldh activity appears absolutely required for pancreas formation (because DEAB-treated embryos lack endoderm gene expression, see above), the weaker phenotype of aldh1a2 mutant zebrafish embryos could be explained if the aldh1a2i26, aldh1a2u11 and aldh1a2um22 alleles represent hypomorphic mutations that maintain some residual Aldh activity.
These differentiated cells will be carrying the different characteristics attributed to exposure of external signals and or genetic mutations that maintain tumourogenic capabilities [ 67].
Recognition sites, on the other hand, may show correlated mutations that maintain the balance between specificity and adaptability (Tokuriki and Tawfik, 2009a, b).
We note that mutations that alter base pairing (C G ↔ A T), which account for ~75% of mutations generated by ENU, are more easily detected by HRM than mutations that maintain nucleotide valence (A T ↔ T A; Figure 4).
In other words, mutations that make the protein or the protein-ligand complex less stable than the starting point are infinitely deleterious, mutations that maintain those stabilities but enable binding of the decoy ligand are somewhat deleterious, and all other changes are neutral.
In conclusion, we predict that ODDD patients which harbour mutations that maintain total Cx43 function in the breast at 50% or better will not suffer from milk production or ejection defects, as appears to be the case for the vast majority of documented ODDD patients to date.
For the limited mutations that maintain T1 characteristics and ET activity, the reduction potential is tuned over a 227 mV range by introducing Met analogues at the axial position, which is far less than the 600 mV range reported in native proteins.
The second method involved extension of this analysis to the rest of the genome, cataloguing mutations that were maintained in a homozygous state.
Consequentially, designed compounds that hide inside some "envelope of function" could be immune to target mutations that maintain native function.
