Human Molecular Genetics, Vol 6, 2135-2139, Copyright © 1997 by Oxford University Press
MD Kaytor, EN Burright, LA Duvick, HY Zoghbi and HT Orr
Nucleotide repeat instability is associated with an increasing number of
cancers and neurological disorders. The mechanisms that govern repeat
instability in these biological disorders are not well understood. To
examine genetic aspects of repeat instability we have introduced an
expanded CAG trinucleotide repeat into transgenic mice. We have detected
intergenerational CAG repeat instability in transgenic mice only when the
transgene was maternally transmitted. These intergenerational instabilities
increased in frequency and magnitude as the transgenic mother aged.
Furthermore, triplet repeat variations were detected in unfertilized
oocytes and were comparable with those in the offspring. These data show
that maternal repeat instability in the transgenic mice occurs after
meiotic DNA replication and prior to oocyte fertilization. Thus, these
findings demonstrate that advanced maternal age is an important factor for
instability of nucleotide repeats in mammalian DNA.
ARTICLES
Increased trinucleotide repeat instability with advanced maternal age
Institute of Human Genetics, University of Minnesota, Minneapolis, MN 55455, USA.
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