CORRELATION OF PHENOTYPE AND CHROMOSOMAL ABNORMALITIES

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This proposed study will combine cytogenetic and molecular techniques to characterize deletions, duplications and marker chromosomes, and to correlate molecular and phenotypic variability. We will test the hypothesis that structurally abnormal chromosomes which appear cytologically similar, are in fact molecularly different, and we will compare possible structural DNA differences to clarify the clinical abnormalities manifested by some of the patients with similar karyotypic abnormalities. Specifically we will: 1) molecularly characterize and determine the chromosomal origin of sex chromosome markers. 2) satellited autosomal markers, with particular emphasis on inv dup (15) chromosomes. 3) the chromosomal origin of autosomal non-satellited markers to determine if any euchromatic material is present in addition to the detected centromeric material 4) the breakpoint and amount of chromosome material missing in chromosome 9p deletion patients 5) the amount of chromosome material deleted/duplicated in patients with subtle deletions/duplications 6) if chromosomal material is missing and the amount of such material deleted or duplicated in patients with other rearrangements not delineated above. In general, three separate groups of individuals with chromosome alterations will be studied: (1) families ascertained via a propositus with phenotypic abnormalities; (2) families with extra or missing chromosomal material, but with no phenotypic abnormalities; and (3) individuals with a chromosome abnormality with a yet unknown phenotype (i.e., ascertained through prenatal diagnosis). A minimum of 100-150 probands with marker chromosomes or de novo rearrangements will be studied.