Ea recombinational hot spot in the mouse major histocompatibility complex maps to the fourth intron of the Ea gene.

Abstract

The majority of recombination events detected within the mouse major histocompatibility complex [MHC} fall into regions of limited physical distance known as hot spots of meiotic recombination. The hot spot associated with the Ea gene appears to be active only in the presence of the p allele carried by the intra-MHC recombinant strain BIO.F03R}. To study the frequency, regulation, and haplotype specificity of recombination at the Ea hot spot, progeny from three different backcrosses involving B10.FCI3R} were screened for recombination events across the MHC using DNA microsatellite markers. Screening of a total of 750 backcross progeny permitted the identification of seven recombinants within the Ea gene. Using restriction site polymorphisms, and sequence-based nucleotide polymorphisms, the recombination breakpoints in all seven Ea recombinants were mapped to two adjacent segments of 71 bp and 346 bp in intron 4 of the Ea gene.

Characterization of a Mouse Recombination Hot Spot Locus Encoding a Novel Non-Protein-Coding RNA

“…The presence of meiotic recombination activity in these hot spots is dependent on the MHC haplotype (46). The Ea hot spot is observed in genetic crosses involving the p haplotype, while the Eb hotspot is active in the b, d, and k haplotypes (22). Similarly, the Psmb9 and Pb hot spots show maximal recombination activity in the cas3 and wm7 and the cas4 and wm7 haplotypes, respectively (18).…”

“…Among the few hot spots that have been mapped to a fine resolution, the human hotspots include (i) minisatellite-associated hot spot MS 32 (20), (ii) the CMT1A/HNPP hot spot associated with hereditary neuropathies (39), and (iii) the major histocompatibility complex (MHC)-associated TAP2 and DNA2 hot spots (19,21). In the mouse, a total of eight hotspots have been identified so far (56), and the ones that have been characterized to a high degree of resolution include (i) the Lmp2/Psmb9 hot spot (32), (ii) the hot spot located in the Eb second intron (57), (iii) the Pb hot spot (18), and (iv) the hot spot located in the Ea fourth intron (22). All the known mouse recombination hot spots have been identified in the MHC region by pedigree analysis, hence not much is known about the hot spot morphology and the recombination processes operating within them, except for the recently published study of the mouse MHC Eb hot spot showing crossover asymmetry and the re-sulting biased gene conversion of markers (56).…”

Mouse Strains with an Active H2-Ea Meiotic Recombination Hot Spot Exhibit Increased Levels of H2-Ea-Specific DNA Breaks in Testicular Germ Cells

“…The H2-Ea (designated Ea here) gene ( Fig. 1) contains a haplotype-specific hot spot in intron 4 (19,24,(27)(28)(29). In a backcross between B10 mice and F 1 animals derived from crossing the strains B10.F(13R) and B10.S(9R), all crossover events observed in the ϳ450-kb H-2 interval (Fig.…”

“…A hot spot region active in the context of one pair of haplotypes may be virtually inactive (a cold spot) in another combination. Thus, strains with an active Ea hot spot show no crossing over at the Eb1 hot spot (19,24). The H2-Ea (designated Ea here) gene ( Fig.…”

“…1), a region rich in genes that control immune function (reviewed in references 14, 31, 38, 45, 49, and 54). Among the best characterized are hot spots associated with loci located in the class II region of the MHC: Eb1 (7,25,57,62), Ea (19,24,27,28), Pb (20,45,59), and Lmp-2 (now called Psmb9) (17,44,46). At each locus, the bulk of the crossover events localize to regions of a few hundred to a few thousand base pairs and recombination rates per unit of physical distance (centimorgan [cM] per megabase) vary from ϳ175 to ϳ2,600 times that expected for DNA segments of the same size based on the mouse genome average rate (0.5 cM/Mb).…”