FUNCTIONAL ANALYSIS OF THE T COMPLEX

Jackson Laboratory, Bar Harbor ME

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Abstract

The t-complex is a 20 cM stretch of DNA found of chromosome 17 in which four inversions, relative to wild type, suppress recombination and, therefore have made it very difficult to map genes within it. Transmission ratio distortion (TRD) and male-specific sterility are two phenomena that are tightly linked and are associated with the mouse t- complex of chromosome 17. Discovered over 50 years ago, these phenomena have yielded to analysis of their molecular basis at an extremely slow rate. Elucidation of the factors involved in sterility may be relevant to determining the causes of idiopathic sterility in human males. We therefore, propose to create deletions centered about two of the loci involved in TRD and sterility in order to: 1. perform complementation tests with the appropriate t-haplotypes to determine if the regions involved in these phenomena can be narrowed to within 300 kb; and, 2. attempt to rescue the phenotypes by the method of pronuclear injection of YAC (or BAC)-borne genomic DNA from the region involved in TRD and sterility.