MOLECULAR ANALYSIS OF THE MAJOR MHC RECOMBINATIONAL HOT-SPOT LOCATED WITHIN THE G7C GENE OF THE MURINE CLASS-III REGION THAT IS INVOLVED INDISEASE SUSCEPTIBILITY

Recombination within the MHC does not occur at random, but crossovers are clustered in hot spots. We previously described a recombinational hotspot within the 50-kb Hsp70.3-G7 interval in the class III region o f the mouse MHC. The parental haplotypes of recombinants with crossove rs in this region represent the majority of the laboratory haplotypes (a, b, d, dx, k, m, p, px, q, s, and u). Using microsatellite markers and sequence-based nucleotide polymorphisms, the breakpoint intervals of 30 recombinants were mapped to a 5-kb-long interval within the G7c gene adjacent to G7a. Recombination within the G7c hot spot does not a ppear to be restricted to certain haplotypes. Sequence motifs that had been suggested to be associated with site-restricted meiotic recombin ation were absent in the vicinity of the G7c hot spot, and hence, thes e sequence motifs are no prerequisite for meiotic recombination. The G 7c hot spot resides in a region to which a number of disease susceptib ility loci have been mapped, including susceptibility to cleft palate, experimental autoimmune allergic orchitis, and chemically induced alv eolar lung tumors. The exact localization of crossovers in recombinant s that have been used in functional studies is important for mapping s usceptibility genes and limits the number of candidate genes.