The long-term objective of this research is a determination of the nature, causes, and effects of chromosomal mutations in mammals. The proposed research involves detailed investigations of the meiotic mechanisms in a mammalian model (deer mice, genus Peromyscus) which displays apparent immunity to the duplication- deletion effects commonly associated with pericentric inversion chromosomal mutations. Proposed studies include examinations of the cellular mechanisms which determine the reproductive effects and inheritance patterns of specifically identified pericentric inversions. It is hypothesized that the immunity to the genetic defects of pericentric inversions in deer mice is mediated by a synaptic mechanism which results in nonhomologous """"""""straight-pairing"""""""" of the inverted segments. It is further hypothesized that this inversion heterosynapsis is functionally related to the location of the chromosomal mutation and the pattern of synapsis of the particular chromosome into which the mutation is incorporated. If such proves to be the case, then the proposed research has the potential to result in a general predictive (and clinically applicable) model from which the effects of classes of chromosomal mutations can be predicted, a priori, from knowledge of the location of the mutations and the pattern of synapsis for each chromosomal pair. Research such as that proposed here is essential to the development of clinical models for the evaluation of the reproductive effects of chromosomal mutations in humans. In the proposed research, chromosomal banding techniques will be used to identify deer mice carrying from one to four pericentric inversions. Meiotic analyses are to entail light and electron microscopic studies of whole cell complements of synaptonemal complexes, and light microscopic evaluations of cross over location and frequency, and patterns of chromosomal segregation into the second meiotic division. The specific objectives of this research include: an analysis of the patterns of synapsis and its effects in individuals carrying inversions, a quantitative analysis of the expected manifestations of associated meiotic abnormalities, and analyses of other cytogenetic phenomena such as the complicating effects of genomic divergence on synapsis and the occurrence of spontaneous chromosomal mutations.
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