Intra-H-2 recombination in t haplotypes shows a hot spot and close linkage of 1tw5 to H-2K

Abstract

The embryonic lethal mutation in the tw5 haplotype is known to map near the H-2K region of the mouse major histocompatibility complex. Additional data obtained by classical genetic methods demonstrate that the tw5 lethal gene is effectively inseparable from H-2K. No recombinants were found between H-2K and tw5 in a sample representing over 1200 mice. On a statistical basis tw5 must be less than 250 kb from the H-2K gene. In the course of these mapping studies we obtained a set of 11 intra-H-2 recombinants. We have analyzed these and three others derived from another experiment to define their breakpoints as precisely as possible. Southern blot analysis with molecular probes to the D, S, I, and K regions of the H-2 complex defines seven recombinations between the D and S regions, two between S and I, none within the I region, and five events between I and K. The last category was studied in finer detail by developing unique copy probes to the I-K boundary region. Two of the five events occurred within probably less than 6 kb of each other: these two recombinants define the centromeric limit of the location of the tw5 gene within the H-2K region. The other three I-K recombinants occurred in at least two other nearby locations. Altogether at least three, and probably all five I-K recombinants fall within a 45 kb recombinational hot spot recently identified in Mus musculus castaneus.