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.
|Yang, Q; Sherman, S L; Hassold, T J et al. (1999) Risk factors for trisomy 21: maternal cigarette smoking and oral contraceptive use in a population-based case-control study. Genet Med 1:80-8|
|Freeman, S B; Taft, L F; Dooley, K J et al. (1998) Population-based study of congenital heart defects in Down syndrome. Am J Med Genet 80:213-7|
|Lamb, N E; Feingold, E; Sherman, S L (1996) Statistical models for trisomic phenotypes. Am J Hum Genet 58:201-12|
|Feingold, E; Lamb, N E; Sherman, S L (1995) Methods for genetic linkage analysis using trisomies. Am J Hum Genet 56:475-83|
|Lorber, B J; Grantham, M; Peters, J et al. (1992) Nondisjunction of chromosome 21: comparisons of cytogenetic and molecular studies of the meiotic stage and parent of origin. Am J Hum Genet 51:1265-76|
|Tanzi, R E; Romano, D M; Berger, R et al. (1992) Sequence-tagged sites (STSs) for a set of mapped markers on chromosome 21. Genomics 14:498-502|
|Lorber, B J; Freeman, S B; Hassold, T et al. (1992) Characterization and molecular analysis of nondisjunction in 18 cases of trisomy 21 and leukemia. Genes Chromosomes Cancer 4:222-7|