Very little information is available on the similarities and differences which might exist between mitotic and meiotic recombination in mammalian cells. As first steps towards determining if different recombinational mechanisms predominate in mitosis as opposed to meiosis we will compare linkae relationships on mitotically and meiotically recombined chromosomes, determine whether or not meiotic and mitotic recombinational hotspots coincide, and whether haplotypes that enhance or suppress meiotic recombination have similar effects on interchromosomal mitotic recombination. We propose to undertake a systematic characterization of the patterns of mitotic recombination on mouse chromosome 17 by using H-2 antigens as selectable markers. Selection of specific H-2 antigen loss variants from H-2 heterozygous cells will be performed by using antibody-mediated complement-dependent cytotoxicity and fluorescence-activated cell sorting (FACS); the use of FACS allows direct selection of variants that are potential recombinants between the K and D regions of H-2. Variant cells will be typed with a variety of Chr 17 DNA probes to determine the relative contribution of interchromosomal mitotic recombination in the formation of variants, as compared with other mechanisms such as mutation, deletion, or chromosome loss that can lead to the same phenotype. Mitotic linkage maps of the proximal portion of Chr 17 will be constructed and compared with meiotic maps derived through ovarian teratoma mapping. Because individual haplotypes differ in gene number, recombination frequencies and site preferences for meiotic recombination it is important to compare mitotic and meiotic maps derived from the same genotype. In addition to the theoretical importance of understanding the patterns of mitotic recombination in mammalian cells, there could also be implications for elucidating mechanisms of oncogenesis by somatic development of homozygosity for certain recessive lethal alleles, for gene therapy in targeting genes to specific sites by homologous recombination, and for assigning chromosomal gene order through somatic cell genetic approaches.
| Henson, V; Palmer, L; Banks, S et al. (1991) Loss of heterozygosity and mitotic linkage maps in the mouse. Proc Natl Acad Sci U S A 88:6486-90 |
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| Carlson, G A; Goodman, P A; Lovett, M et al. (1988) Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time. Mol Cell Biol 8:5528-40 |
