The purpose of the proposed research is (1) to study the effect of different Robertsonian chromosomes in the mouse on meiotic pairing and genetic recombination, (2) to utilize these Robertsonian chromosomes to produce a mutagen-testing system, (3) to induce and study models of human chromosomal aberrations, (4) to use Robertsonians in the analysis of linkage in the mouse, and (5) to consolidate and maintain Robertsonians in homozygous stocks. Meiotic pairing will be examined by examining synaptonemal complexes in heterozygotes and between Robertsonians with the same chromosomal constitution but independent origins. Effect on recombination will be determined by ascertaining recombinational distances with and without Robertsonians. Comparison of the two kinds of data for individual chromosomes will show if there is a cause and effect relationship. The test system will involve tying up large portions of the mouse genome for detection and recovery of induced lethal and detrimental mutations by combining paracentric inversions, which reduce or prevent the recovery of cross-over products in the inverted segment, with Robertsonians, which suppress crossing over near the centromere. Chromosomal aberrations will be produced by triethylenemelamine treatment of Robertsonian-carrying mice. An integral part of the proposed study will be the consolidation of an existing large colony of mice carrying a variety of Robertsonian chromosomes into homozygous stocks both useful for the proposed research and to other investigators. This will include reconstruction of a mouse stock in which 18 of the 19 telocentrics are involved in a Robertsonian.
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