There are several interrelated phases to the study. The first is to determine the parental origin of the extra chromosome in a large number of cases by using standard or modified quinacrine fluorescent banding technique (Q banding). In addition, DNA will be extracted from the cells of the patients and their parents for analysis at either Emory University or the University of Michigan. Chromosome 21 specific probes recognizing highly polymorphic sequences (RFLPS) will be used to determine the parental origin of the extra chromosome 21 and probes for distal loci will be used to study the rate of recombination between the two chromosomes 21 derived from the same parent. This will help to establish whether decreased or increased recombination may play a role in producing trisomy 21. In addition, these studies will contribute to the construction of a genetic map of chromosome 21. An epidemiology study of pre-conceptual health factors which may increase the risk of Down syndrome is planned. Knowledge of the parent in which the nondisjunction event occurred will increase the chance of identifying factor(s) which play an etiologic role in one or more of the specific groups, categorized according to the time or the nondisjunctional event. Finally an attempt will be made to ascertain whether there is a differential effect on the Down syndrome phenotype which is dependent on whether the extra chromosome is maternal or paternal in origin.

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Emory University
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