To add to the body of knowledge that is growing about the molecular and genetic basis for aneuploidy, we conducted a multidimensional project. In the first part of the study, the primary objective was to determine if there is a higher proportion of unbalanced chromosomal complements in nonviable compared to viable sperm. To meet this objective, sperm aneuploidy levels in ten males were scored, using a fluorescent in situ hybridization (FISH) technique, and compared to allow for the detection of potential differences specific to sperm viability status, chromosomes, or males.; For the second part of the project, the primary aims were to assess the genetic influence on human sperm morphology and its possible association with sperm aneuploidy levels. To achieve these aims, the aneuploidy levels in sperm from 23 monozygotic (MZ) and 5 dizygotic (DZ) twin pairs were determined, using FISH, and the proportions of sperm with abnormal forms (head, midpiece and tail defects) were assessed.; The final goal of the study was to evaluate the variability in clinical outcome and the mechanism(s) underlying mosaic Down syndrome (MDS). To attain this goal, we studied 56 individuals with MDS (along with their parents and siblings). The information collected from the study participants included (1) the proportion of lymphocytes (cultured and uncultured) and buccal mucosa cells that were trisomic; (2) physical and developmental outcome; and (3) cellular timing of the malsegregation resulting in the observed mosaicism. No significant difference in the percentage of cells having a trisomic complement, using FISH, was seen in cultured compared to uncultured lymphocytes. In contrast, the proportion of trisomic buccal mucosa cells was significantly different from that of lymphocytes, with a trend toward higher levels of trisomic cells being seen in the buccal preparations. An assessment of the medical records of individuals with mosaic Down syndrome showed a trend toward increased severity in the individuals having higher levels of trisomic cells. Differences in the chromosomal malsegregation events leading to mosaicism, which were assessed using DNA markers, were also seen, and included cases arising from (1) a meiotic and mitotic nondisjunction event; or (2) a single mitotic error. (Abstract shortened by UMI.)
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