Research is designed to yield new insights into basic mechanisms of heredity in higher organisms. Projects investigate, from several avenues of approach, the nature of cellular structures and processes involved in homologous chromosome pairing, genetic recombination, crossover interference, the maintenance of chiasmate association, and chromosome distribution to gametes. Techniques include cytogenetic engineering, laboratory experimental treatment, and cytological and ultrastructural observation. The organism selected for study offers a unique combination of excellence of meiotic cytology, an array of available meiotic mutants, chromosome rearrangements and polysomics, a very good genetic map, and probability of general applicability of findings. --- Specific projects are focused on: (1) evaluation of differential capabilities in specific chromosome regions for pairing which is effective for crossing over, based on cytological observations of a variety of chromosome rearrangements; (2) identification of chromosomal positions of sites which may be specialized for alignment pairing of homologues, utilizing improved techiques for surface spread chromosome preparations from special trisomic materials and EM observation; (3) exploration of a possible indirect role for cytoskeletal components in early phases of homologue alignment pairing, by means of ultrastructural and indirect immunofluorescent study as well as chemical effect experimentation; (4) evaluation of close association of homologues at premeiotic mitotic prophase as a possible advance form of homologue interaction in preparation for synapsis, using observation of chromosomes marked by conspicuous rearrangement changes; (5) ultrastructural comparison, with image processing and quantitation techniques, of mutant desynaptic and normal material at meiotic prophase for possible differences in interrelationships between SC components and sister chromatid association in this chiasma maintenance defective mutant. --- This research is expected to contribute to fundamental understanding of problems of great human concern. Basic knowledge of the mechanism of chromosome pairing and recombination may contribute not only to understanding of vital processes of meiosis, but also to understanding of the generation of antibody diversity by the immune system and the etiology of some malignancies. The nature of the chiasmate association and its occasional failure has special relevance for understanding and preventing initial steps in the production of Downs syndrome and other human aneuploid abnormalities.
