The secondary factors modulating the mitochondrial DNA (mtDNA) LHON mutations still remain largely undefined, although the gender bias has been linked to the synergistic influence of visual-loss susceptibility loci on the X-chromosome (Hudson et al., 2005; Shankar et al., 2008).
Although the somatic gene mutations that drive CIN remain largely unknown, it is clear that no single gene is responsible for the CIN phenotype observed in CRCs.
As in the case of replication timing, the differences in mutation rate by expression level remain largely consistent within mutation type and nucleotide context.
However, the mechanisms of generating these mtDNA mutations in the carcinogenic process remain largely unknown, although it is known that mtDNA is subjected to continuous oxidative attack by free radicals [ 9].
In this context, there is an increasing recognition that stochastic processes regulate highly predictable patterns of gene expression in developing organisms, but the implications of stochastic gene expression for understanding phenomena such as genomics mutations and copy number variations remain largely unexplored [ 2].
Previous studies have indicated that the development of TCC involves multiple steps [ 2- 4], but the key mutations and how this process occurs remain largely unknown.
However, a few exceptions aside, the functional consequences of those mutations have remained largely elusive.
However, the molecular mechanisms by which the mutations in these phosphatases induce such diseases remain largely unknown [ 19, 24].
The exact functional consequences of these spliceosomal mutations in MDS pathogenesis and other hematological malignancies remain largely unknown, and are being intensely investigated [ 9].
However, the large agricultural and informal sectors remain largely unregulated.
