Of the 7 mutations (SNPs discovered only in the NAF and not present in the blood) noted between all samples, three were associated with known problematic features of MCv2 at nucleotide positions 9179, 9914, and 11719 (Table 3).
Importantly, in patients with viral breakthrough resistance associated variants (RAVs) were predominantly identified within NS3-4A while a resistance mutation in NS5B was discovered only in a single patient (S282T).
Several family studies have shown a strong polygenetic predisposition for AF but, so far, most of the linkage analysis and candidate gene studies have discovered only monogenic, rare, deleterious mutations.
For 7/9 new C. briggsae ΔmtDNA types reported here, the elements were discovered only once in a single experimental nematode lineage; all of these cases likely represent de novo deletion mutation events that occurred during the experiment.
It was discovered only months later.
After validation with ultra deep re-sequencing of fourteen mutations discovered in the original exome sequencing we found only one mutation to be unique in the CSCs and that in a low frequency (4.8%).
We grouped mutations into objects because most mutations discovered within the thermal stress experiment were found in only a single clone, and hence provided no basis for associating genotype with phenotype.
However, a closer look at the mutations discovered by Jones et al. through exome sequencing [ 10] revealed that only KRAS and BRAF were recurrently mutated in LGSC.
Numerous methods have been applied to the mutations discovered in these sequencing projects in an attempt to identify the causal mutations, but the majority of this analysis has been based upon methods that can only identify deleterious mutations [1] [5].
If this FALS-SALS percentage ratio were to remain the same when 100% of FALS-causing mutations are discovered, by extrapolation only 16% of SALS patients will harbour ALS-causing mutations.
