Huntington disease expansion mutations in humans can occur before meiosis is completed.

Abstract

Single-molecule DNA analysis of testicular germ cells isolated by laser capture microdissection from two Huntington disease patients showed that trinucleotide repeat expansion mutations were present before the end of the first meiotic division, and some mutations were present even before meiosis began. Most of the larger Huntington disease mutations were found in the postmeiotic cell population, suggesting that expansions may continue to occur during meiosis and/or after meiosis is complete. Defining the germ-line cell compartments where the trinucleotide repeat expansions occur could help to elucidate the underlying mechanisms of instability.