NONDISJUNCTION OF CHROMOSOME-15 - ORIGIN AND RECOMBINATION

Thirty-two cases of uniparental disomy (UPD), ascertained from Prader- Willi syndrome patients (N=27) and Angelman syndrome patients (N=5), a re used to investigate the pattern of recombination associated with no ndisjunction of chromosome 15. In addition, the meiotic stage of nondi sjunction is inferred by using markers mapping near the centromere. Tw o basic approaches to the analysis of recombination are utilized. Stan dard methods of centromere mapping are employed to determine the level of recombination in specific pairwise intervals along the chromosome. This method shows a significant reduction in recombination for two of five intervals examined. Second, the observed frequency of each recom binant class (i.e., zero, one, two, three, or more observable crossove rs) is compared with expected values. This is useful for testing wheth er the reduction in recombination can be attributed solely to a propor tion of cases with no recombination at all (because of asynapsis), wit h the remaining groups showing normal recombination (or even excess re combination), or whether recombination is uniformly reduced. Analysis of maternal UPD(15) data shows a slight reduction in the multiple-reco mbinant classes, with a corresponding increase in both the zero- and o ne-recombinant classes over expected values. The majority, more than 8 2%, of the extra chromosomes in maternal UPD(15) cases are due to meio tic I nondisjunction events. In contrast, most paternal UPD(15) cases so far examined appear to have a postzygotic origin of the extra pater nal chromosome.