The work described in this proposal is designed to examine the degree of genetic polymorphism in a variety of major histocompatibility complex (MHC) linked and non-linked enzyme loci. The objectives of the proposal are (1) to establish whether or not those loci associated with the rat MHC exhibit a higher degree of genetic variation than those coded for by other, non-MHC, linkage groups, (2) to establish the presence or absence of significant linkage disequilibrium between alleles at loci within homologous chromosomal segments shared between rodents and man and, (3) to detect and characterize new enzyme variants potentially linked to the rat MHC (RT1 complex) for use as marker genes in genetic studies of this important complex. The research work will be conducted by systematically screening blood and tissue samples collected from widely-separate populations of wild rats. Multiple sites at each locus compared within the rat populations and to comparable studies in other species. New alloenzyme variants will be characterized and their chromosomal linkage relationships established whenever possible. The research work outlined in this proposal addresses three important problems. The first is whether or not the restricted degree of polymorphism and linkage disequilibrium observed in the rat MHC is unique or are also seen in unrelated linkage groups. The results of these experiments may have a substantial impact on theories that relate to the requirement for high levels of polymorphism to explain the function of the MHC. Secondly, we seek to determine if linkage disequilibrium can be invoked as a mechanism to explain the retension of homologous chromosomal segments. The retension of large, homologous chromosomal segments between species is well recognized but it remains to be established whether or not these segments are maintained by chance or by active selection. Third the discovery of new variants for enzymes linked to the MHC can be of important use in establishing the structure and gene order of loci within the RTl complex of the rat.
