Molecular characterization of a meiotic recombinational hotspot enhancing homologous equal crossing‐over.

We have cloned and sequenced a meiotic recombinational hotspot between the A beta 3 and A beta 2 genes in the major histocompatibility complex (MHC) of the mouse. This recombinational hotspot in the Mus musculus castaneus cas3 haplotype was previously localized to a region of 9.5 kb of DNA in which five independent crossing‐over events occurred at the unusually high frequency of 0.6%. Aside from cas3, the hotspot appears to be absent in many other MHC haplotypes. We have now confined the five recombinational breakpoints to a stretch of 3.5 kb of DNA. From the nucleotide sequence around the recombinational breakpoints, determined in the parental cas3 and b haplotypes as well as for two recombinant haplotypes, we show that the two recombinant haplotypes were generated by homologous equal crossing‐over and place the breakpoints within two non‐overlapping stretches of 10 and 36 bp, respectively. Comparison of the DNA sequences of the hotspot‐positive cas3 and the hotspot‐negative b haplotypes reveals a number of differences, in particular, a CAGA‐repeat sequence which is present in CAS3 in six, but only four copies in C57BL/6 DNA. This repeat sequence is reminiscent of one in a previously characterized hotspot in the E beta gene.