One of the most promising therapeutic strategy for DMD aims to convert an out-of-frame mutation into an in-frame mutation, which would give rise to internally deleted, but still functional dystrophin (1, 2).
There was some variation in allelic diversity by locus (Table S2) but it was generally low, with the total number of STs (451) approximately equal to the number of alleles (410) suggesting that the variation in genotypes results more from re-assortment of existing alleles than generation of new ones by point mutation which would give more alleles per locus.
For unlinked sites, nonsynonymous mutations would have much shorter lifetimes to fixation than synonymous changes, given their substantial level of (positive or negative) selection inferred below.
Selection for individuals with mutations in these features would give rise to adaptation of the distribution without changing highly-conserved network proteins.
In equilibrium, the variance ratio between penta/hexa and tri/tetra STRs times a mutation rate of tri- and tetranucleotide markers would give a mutation rate of penta- and hexanucleotide STRs.
However in our gain of function mutant, mCx31, the other end of the bridge is K104 and the mutation R104K in Cx26 would give relatively little further information as we already know that a lysine at this position can substitute for the arginine.
Number of patients in whom each mutation was found, should be indicated – this would give an idea about any preponderance of specific mutations in this population.
For example, with intratumoral LOH, and mutation of the remaining allele, dHPLC screening would give a false negative result.
Of the remaining 63 mutable positions of the genetic code, 58 would give rise to 26 amino acid substitutions (mis-sense mutations) and 5 would result in stop codons (nonsense mutations).
For example, with real data one could explore whether some particular threshold for Δ DS would give significant separation of harmless versus harmful mutations.
