Utilizing material from chromosomally abnormal fetuses and live-born individuals and their parents, we intend to combine cytogenetic and molecular techniques to: 1) Study the mechanism of origin of sex chromosome trisomy. We will determine the parent and meiotic stage of origin of the 47,XXY, 47,XYY, and 47,XXX conditions, determine the relationship between parental origin of trisomy and parental age, and test the hypothesis that abnormally high or low levels of recombination contribute to non-disjunction involving the X and Y chromosome. 2) Study the mechanism of origin of sex chromosome monosomy. We will determine the parental origin of the error leading to the 45,X condition, and evaluate the hypothesis that mosaicism for a second sex chromosome is responsible for the survival of most, if not all, liveborn 45,X conceptuses. 3) Study the mechanism of origin of trisomy 21 in leukemic Down Syndrome individuals to determine if a correlation exists between the timing or parental source of non-disjunction and predisposition to leukemia. 4) Evaluate the hypothesis that the human X chromosome is imprinted. Specifically, we will combine DNA polymorphism analysis with studies of methylation to evaluate inactivation patterns of maternally and paternally derived X chromosome in embryonic and extra-embryonic tissues, and compare the phenotype and X-linked methylation patterns of 45,X conceptuses having a single maternally derived X chromosome with those having a single paternal X.
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