Repeat instability: mechanisms of dynamic mutations

Abstract
Since the identification in 1991 of repeat instability as a disease-causing mutation, gene-specific repeat instability is now known to be the mutational cause of at least 40 neurological, neurodegenerative and neuromuscular diseases. Repeat instability is a dynamic mutation and is defined by both cis-elements and trans-factors. Both germline (parent-to-offspring) and tissue-specific somatic instability occurs. There are unique and common effectors for the instability of different repeat sequences, although each disease or locus is unique. Replication, repair and recombination contribute to repeat instability, either separately or in combination. Extrapolation of repeat instability data from model systems must take into account the limitations of the model and observations from human patients.

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