Minisatellites provide one of the most experimentally tractable system
s for studying tandem repeat instability in man. Analysis of mutation
processes has been greatly aided by the development of single molecule
methods for recovering de novo mutants, and of techniques for explori
ng allele structure in detail. Application of these approaches to man
has shown that minisatellites do not primarily mutate by processes suc
h as replication slippage and unequal crossover intrinsic to the tande
m repeat array. Instead, germline repeat instability is largely regula
ted by cis-acting elements near the array and involves unexpectedly co
mplex processes of gene conversion, of potential relevance to the biol
ogy of meiosis. These processes can be explored both in humans and, in
principle, in transgenic mouse models of human repeat instability.