On the other hand, there is abundant evidence of deleterious mutations, varying in severity of effect from strongly deleterious to very mild, particularly in regions conserved in the outgroup taxa, indicating a history of persistent purifying selection.
Ample studies have reported mutations in p53 in oesophageal carcinomas, with mutation frequencies varying from 40 to 90% (Jankowski et al, 1999; Mandard et al, 2000; Wijnhoven et al, 2001; Jenkins et al, 2002).
Studies have reported a prevalence of TP53 mutations in ESCC varying from 35 to 89%, depending on the geographical region.
The emerging pattern is that there are relatively few frequently mutated genes, (most of these already known) and a very large number of rare mutations, often highly varying from one case to another [ 22].
From analyses of copy number variants (CNVs) and exome sequencing, it is now estimated that mutations in hundreds of genes can substantially increase the risk of developing ASD, the predisposing mutant genes varying from one individual to another [ 1- 5].
This only leads to a biochemical defect of the respiratory chain when a critical threshold level is exceeded, with the precise amount varying from mutation to mutation.
Early population-based studies reported BRCA1 mutation rates in OC patients varying from 1.9 to 7.2% [ 43– 43].
Previous reports describe p53 base changes in 15 50% of RA FLS lines, with a frequency of mutations within the p53 cDNA pool varying from 0%to30%0% [ 8, 23, 29].
While species-specific differences in germline mutation rate have been attributed to various factors, varying from generation time to metabolic rate, the most likely explanation remains differences in genome maintenance (Thomas & Hahn, 2014).
