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

^*Molecular and Computational Biology Program and ^‡Department of Pathology, University of Southern California, Los Angeles, CA 90089-1340; ^§Venezuela Huntington Disease Project, Hereditary Disease Foundation, New York, NY 10032; and ^¶Departments of Neurology and Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY 10032

Edited by Stanley M. Gartler, University of Washington, Seattle, WA, and approved May 7, 2003 (received for review March 10, 2003)

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.

Footnotes

↵ ∥ To whom correspondence should be addressed at: Molecular and Computational Biology Program, University of Southern California, 835 West 37th Street, Los Angeles, CA 90089-1340. E-mail: arnheim{at}usc.edu.
↵ † S.-R.Y. and L.D. contributed equally to this work.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: HD, Huntington disease; TNR, trinucleotide repeats; LCM, laser capture microdissection.