RT Journal Article
SR Electronic
T1 Non-Mendelian transmission at the Machado-Joseph disease locus in normal females: preferential transmission of alleles with smaller CAG repeats.
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 234
OP 236
DO 10.1136/jmg.34.3.234
VO 34
IS 3
A1 D C Rubinsztein
A1 J Leggo
YR 1997
UL http://jmg.bmj.com/content/34/3/234.abstract
AB Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is a neurodegenerative disorder which is associated with a CAG repeat expansion in the MJD1 gene on chromosome 14q32.1. A recent study reported an excess of transmission of disease chromosomes relative to normal chromosomes from affected fathers, while this phenomenon was not observed in female meioses. These data were compatible with meiotic drive. We investigated the transmission of alleles with larger versus smaller CAG repeat numbers in the MJD1 gene in normal heterozygotes from the 40 CEPH families. Our data suggest that there was no segregation distortion in male meioses, while the smaller CAG allele was inherited in 57% of female meioses (p < 0.016). The pattern of inheritance of smaller versus larger CAG alleles at this locus was significantly different when male and female meioses were compared (p = 0.0139). While previous data suggest that meiotic drive may be a feature of certain human diseases, including the trinucleotide diseases MJD, myotonic dystrophy, and dentatorubral-pallidoluysian atrophy, these data are compatible with meiotic drive also occurring among non-disease associated CAG sizes.