Under this model, single-repeat mutations have a probability of p whereas multirepeat mutations (length of change ≥1 repeat) have a probability of 1 − p. For multirepeat mutations, the distribution of step size, | i − j|, is given by a truncated geometric distribution γ g, i, j).
The implemented microsatellite models are based on the replication slippage mechanism and focus on three properties of microsatellite mutation: length dependency of mutation rate, mutational bias toward expansion or contraction, and number of repeat units changed in a single mutation event.
In the same study, considering the relative caudate glucose metabolism along with CAG mutation length increases the regression coefficient for prediction of AO, indicating that glucose metabolism is a good predictor of disease onset (10, 11).
Subsequent studies have borne this hypothesis out by evaluating neuropathologic anatomical feature in individuals that have a size mosaic for the Fragile X Premutation and Full Mutation (i.e., they express alleles with Premutation and alleles with Full Mutation length mutations).
Interestingly, a 5-year follow-up study on asymptomatic HD gene carriers found that the caudate glucose metabolism was significantly decreased in patients that became symptomatic in the course of the study, and this change was not correlated with the CAG mutation length (10).
As shown, expanded FMR1 repeats of pre-mutation lengths are retained in the nuclei of FXTAS post-mortem brains and in the brains of transgenic mice that express 98 CGG repeats.
We found that only 3 out of 14 α-helical coiled coils showed point mutations and/or length polymorphisms.
In order to estimate the mutation rate, we need to know, in addition to the number of mutations, the length of the region contributing data and the number of years or generations separating the chromosomes.
These peculiar sequences show high rate of reversible mutation in length, ranging from 10−7 to 10−3 number of mutations per generation, which is higher than the average genomic rate of point mutations normally evaluated at 10−8 10−9 [ 3].
Surprisingly, disease duration is independent of the mutation's length.
Combinations of mutation with length of 2 and occurring on the same viral genome are then selected.
