Use of restriction fragment length polymorphic probes in the analysis of Down's syndrome trisomy

Summary Restriction fragment length polymorphic probes are being used more frequently in the molecular analysis of Down's syndrome and in the origin of nondisjunction in the syndrome. The type of information gained from RFLPs overlaps but differs from the information from cytogenetic heteromorphisms. From the allele frequencies of commonly available probes we have derived the expected frequencies of all matings in the population. Each mating has been defined and partitioned to show the genotypes and phenotypes expected, with numerical values based on studies with heteromorphisms. From this we show how the various phenotypes can be used to calculate the origin of nondisjunctions and their expected frequencies. Further, an alternative method is outlined for mapping the distance between a probe and its centromere based on the distortion, caused by crossing-over, of the expected 1st to 2nd division nondisjunction ratio. Finally, we discuss prospects for various uses of probes in the analysis of Down's syndrome.