THE EFFECT OF Y-CHROMOSOME ALPHA-SATELLITE ARRAY LENGTH ON THE RATE OF SEX-CHROMOSOME DISOMY IN HUMAN SPERM

Trisomy is the leading known cause of mental retardation and pregnancy loss in humans, yet virtually nothing is known of the underlying nond isjunctional mechanisms. Since studies of other organisms suggest an a ssociation between centromere size or sequence and meiotic nondisjunct ion, we recently initiated studies to examine the effect of centromere size variation on human nondisjunction. In the present report, we sum marize studies correlating variation in the size of the Y-chromosome c entromere with sex chromosome nondisjunction. In one set of studies, w e used pulsed-field gel electrophoresis to estimate Y-chromosome alpha -satellite array lengths in normal males, and correlated these values with Y-chromosome sperm disomy levels as determined by fluorescence in situ hybridization. In a second set of studies, we determined the Y-c hromosome alpha-satellite array length of 47,XYY males, since the kary otypes of these individuals are a consequence of Y chromosome nondisju nction. Neither set of studies provided evidence for an effect of Y-ch romosome alpha-satellite array length on Y-chromosome nondisjunction. Thus, if there is an association between Y-chromosome centromere size and nondisjunction, the effect is subtle and below the detection level s of the present study or involves extreme size variants that were not represented in the present study population.