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 s uggested as being responsible for maintaining the frequency, in the hu man population, of DM chromosomes capable of expansion to the disease state. In order to test this hypothesis, we have studied samples of si ngle sperm from three individuals heterozygous at the DM locus, each w ith one allele larger and one allele smaller than 19 CTG repeats. To g uard against the possible problem of differential PCR amplification ra tes based on the lengths of the alleles, the sperm were also typed at another closely linked marker whose allele size was unrelated to the a llele size at the DM locus. Using statistical models specifically desi gned to study single-sperm segregation data, we find no evidence of me iotic segregation distortion. The upper limit of the two-sided 95% con fidence interval for the estimate of the common segregation probabilit y 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 d istortion at the myotonic dystrophy locus must result from events foll owing sperm ejaculation. The mathematical models developed make it pos sible to study segregation distortion with high resolution by using sp erm-typing data from any locus.