Gene organization and recombinational hotspots in the murine major histocompatibility complex.

By chromosome walking in the major histocompatibility complex (MHC) of the BALB/c mouse, we have linked the K region to the I region at the molecular level. Forty-nine overlapping cosmid clones define a stretch of about 600 kb of DNA containing 2 class I and 7 class II genes. Eleven independent recombination events were mapped between the K and the I region marker loci by Southern blot analysis of polymorphic restriction sites. Eight of these events involved crossing-over, at an unusually high frequency of 0.6%-1.5% between genes from Mus musculus castaneus and laboratory mouse strains, and they were confined to two small stretches of DNA. We conclude that recombination hotspots are present at these positions in the two M.m. castaneus MHC haplotypes tested. In contrast, several MHC haplotypes of laboratory mice appear to lack those hotspots.