Analysis of meiotic segregation, using single-sperm typing: meiotic drive at the myotonic dystrophy locus.
Meiotic drive at the myotonic dystrophy (DM) locus has recently been suggested as being responsible for maintaining the frequency, in the human population, of DM chromosomes capable of expansion to the disease state. In order to test this hypothesis, we have studied samples of single sperm from three individuals heterozygous at the DM locus, each with one allele larger and one allele smaller than 19 CTG repeats. To guard against the possible problem of differential PCR amplification rates based on the lengths of the alleles, the sperm were also typed at another closely linked marker whose allele size was unrelated to the allele size at the DM locus. Using statistical models specifically designed to study single-sperm segregation data, we find no evidence of meiotic segregation distortion. The upper limit of the two-sided 95% confidence interval for the estimate of the common segregation probability for the three donors is at or below .515 for all models considered, and no statistically significant difference from .5 is detected in any of the models. This suggests that any greater amount of segregation distortion at the myotonic dystrophy locus must result from events following sperm ejaculation. The mathematical models developed make it possible to study segregation distortion with high resolution by using sperm-typing data from any locus.
Leeflang
E P
EP
Department of Biological Sciences, Molecular Biology Program, University of Southern California, Los Angeles, USA.
McPeek
M S
MS
Arnheim
N
N
D000328:Adult; D000483:Alleles; D006580:Genetic Carrier Screening / Q000379:methods; D006801:Humans; D008297:Male; D008540:Meiosis; D008954:Models, Biological; D009223:Myotonic Dystrophy / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013094:Spermatozoa / Q000166:cytology*