French Machado-Joseph disease patients do not exhibit gametic segregation distortion: a sperm typing analysis.

R. P. Grewal, G. Cancel, E. P. Leeflang, A. Durr, M. S. McPeek, D. Draghinas, X. Yao, G. Stevanin, M.-O. Alnot, A. Brice, N. Arnheim
Human Molecular Genetics. 1999-09-01; 8(9): 1779-1784
DOI: 10.1093/hmg/8.9.1779

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1. Hum Mol Genet. 1999 Sep;8(9):1779-84.

French Machado-Joseph disease patients do not exhibit gametic segregation
distortion: a sperm typing analysis.

Grewal RP(1), Cancel G, Leeflang EP, Dürr A, McPeek MS, Draghinas D, Yao X,
Stevanin G, Alnot MO, Brice A, Arnheim N.

Author information:
(1)Program in Molecular Biology, SHS 172, 835 West 37th Street, University of
Southern California, Los Angeles, CA 90089-1340, USA.

Segregation distortion has been reported to occur in a number of the
trinucleotide repeat disorders. On the basis of a sperm typing study performed in
patients of Japanese descent with Machado-Joseph disease (MJD), it was reported
that disease alleles are preferentially transmitted during meiosis. We performed
a sperm typing study of five MJD patients of French descent and analysis of the
pooled data shows a ratio of mutant to normal alleles of 379:436 (46.5:53.5%),
which does not support meiotic segregation distortion. To confirm these results,
sperm typing analysis was also performed using a polymorphic marker, D14S1050,
closely linked to the MJD1 gene. Among 910 sperm analyzed, the allele linked to
the disease chromosome was detected in 50.3% of the samples and the allele linked
to the normal chromosome was found in 49.6% of the sperm. The difference in
frequency of these two alleles is not significant ( P = 0.8423). Likelihood-based
analysis of segregation distortion in the single sperm data using the SPERMSEG
program also showed no support for segregation distortion at the gamete level in
this patient population. The previous report on the Japanese patients also
suggested that disease allele stability may be influenced by a trans effect of an
intragenic polymorphism (987 G/C) in the wild-type allele. All of the French
patients were heterozygous for this polymorphism. However, analysis of the
variance in repeat number in sperm from the French MJD patients overlapped
significantly with the variance in repeat number observed in the C/C homozygous
Japanese patients.

DOI: 10.1093/hmg/8.9.1779
PMID: 10441343 [Indexed for MEDLINE]

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