Comparisons between wild-type and mutator lines are made to reveal what types of pre-mutation errors are most commonly made during the DNA replication process, and which pre-mutations are preferentially fixed by a functional mismatch-repair (MMR) system.
In the case of trinucleotide repeat diseases, normal variation in a mean repeat size stands in contrast to unbridled instability (expansion) once a threshold size for a pre-mutation has been exceeded.
Men with premutations will almost always pass pre-mutations to all of their daughters.
Therefore, intermediate alleles might rather be considered as predisposing alleles for further stepwise expansion over probably many generations instead of pre-mutations.
The substitution spectra for wild-type and MMR-deficient lines (Fig. 2) differed substantially, demonstrating that the MMR system corrects different classes of pre-mutations with different efficiencies.
Most of these mismatches (pre-mutations) are identified and returned to the ancestral state by the MMR system of the cell, but a small proportion are resolved to the derived state and become true mutations.
Rate comparisons for P. aeruginosa indicate that 99.6%% of raw pre-mutations (BPMs and indels) are corrected by the MMR system before they become stably incorporated into the genome.
Intermediate alleles with 38 50 triplets are not disease causing but they are considered as "pre-mutations"; repeats with alleles 51 100 are protomutations, both of which show increased instability towards expansions.
Table S4.A Cancer occurring in the Cohort of 241 women with FMR1 pre-mutation and full-mutation.
B Cancer incidence in the Cohort of 199 women with FMR1 pre-mutation and full-mutation Table S5.
Unlike the full mutation in FXS, this smaller expansion – known as "pre-mutation" – does not induce FMR1 gene silencing.
