Mouse t haplotypes are naturally-occurring, highly variant forms of a region of mouse chromosome 17 that has multiple and interacting loci with profound effects on embryogenesis and sperm differentiation. The t haplotypes maintain themselves as discrete genomic entities through recombination suppression, and these chromosomal units are propagated through wild populations by a male-specific transmission ratio distortion in their favor. Our understanding of t haplotypes has undergone radical changes over the last 5 years, and it is now possible to focus research efforts in attempts to answer specific questions concerning these selfish chromosomal units. First, what is the origin of t haplotypes? It should be possible to answer this question by comparative DNA sequence analysis of single copy t complex genomic clones from many individuals of several related mouse species. Second, what is the genomic organization of t haplotypes? This question will be approached with the use of the low-copy number t genomic clones as polymorphic molecular markers in a classical recombination analysis. Third, what is the nature of t haplotype-associated lethal genes? Fine resolution classical mapping of 2 lethal genes localized within or near the H-2 complex will be continued with an ultimate goal of directly cloning these genes starting with available H-2 region probes. Fourth, how do t haplotypes affect sperm differentiation? cDNA cloning of t complex gene products will be pursued, and mice with appropriate compound t genotypes will be constructed to determine gene interaction in transmission ratio distortion. In the process of studying one small chromosomal region, it is hoped that our general understanding of the organization, expression, and evolution of the mammalian genome will be enhanced.
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