ABSTRACT
The dynamic nature of the trinucleotide repeat mutations that cause these diseases provides a molecular explanation for these phenomena. In particular, there has been much interest in the mutational processes of trinucleotide repeats associated with disease genes, as these can give clues about the evolution and population genetics of the diseases and inform our understanding of microsatellites in general. A number of transgenic mice have been created which contain human trinucleotide repeat genes or fragments of these genes with expanded repeat tracts. Interestingly, similar-sized repeat expansions in the same construct in different lines show markedly differing levels of instability. This may suggest that the degree of instability may be related to the site of integration of the transgene. Preliminary single sperm analysis of HD chromosomes supports this intriguing possibility and the existence of alleles with greatly differing mutabilities has also been documented among minisatellites.
