Another sample, B4 was interesting as the HRM data indicated a clear mutation but the sequencing data showed the mutation at the lower limit of detection.
In future, it is likely that, where a clear mutation has been associated with a genetic rheumatic or orthopedic disease, a gene therapy approach will be tried [ 43].
There are no clear mutational hotspots, and mutations are rarely recurrent among the usually compound heterozygous patients.
However, if only one nonsynonymous mutation had been observed, the actual frequency of mutation is not clear since mutation frequencies of 0.5, 1, or 2 mutations per 10000 clones, a range of 400%, are all realistic and compatible with the given data.
It is still possible that in smaller populations, stochastic effects such as Muller's ratchet may occur, and allow sex to more effectively clear detrimental mutations in the absence of beneficial mutations [ 27].
Together with the above observation that mutation rate differs at different genomic locations, it is clear that mutations do not occur randomly, but are influenced by both local nucleotide context and genomic position.
Due to these regulatory and functional differences, it was not clear whether mutations in SIS7/NCED3/STO1 would cause a sugar-insensitive phenotype, as had been previously shown for mutations in other ABA biosynthetic genes [ 11, 13, 16].
Therefore, clear driver mutations are seen in different cancer types due to the impact of that specific mutation in the cell of origin of that particular tumour.
But it is not clear why mutations in this gene, which seems to be involved in metabolism — possibly to detoxify chemicals — can cause tumors or how these tumors form.
