Inversion in the H-2 complex of t-haplotypes in mice.
Mouse t-haplotypes demonstrate strong linkage disequilibrium between t-lethal genes and specific H-2 types, presumably a result of recombination suppression between t and normal chromosomes. The observation of free recombination occurring between two complementary t-haplotypes suggested a chromosomal mismatch between t and normal chromosomes. Recent data showing the H-2 complex to be misplaced relative to two other markers, T and tf, in t-haplotypes suggested that chromosomal rearrangement in t-haplotypes might be the basis for their 'mismatch' with the normal chromosome. Here, to analyse the molecular nature of the rearrangement, we have cloned a polymorphic H-2 class I restriction fragment, which had previously been shown to map centromeric to the serologically defined H-2 complex in t-haplotypes. Genetic mapping studies show that this cloned t-DNA is homologous to the H-2 D region of wild-type chromosomes, and that the E alpha Ia gene maps telomeric to this DNA fragment in t-haplotypes, in contrast to its orientation in wild-type chromosomes. These results give molecular evidence for an inversion of H-2 in t-haplotypes, which may be at least partially responsible for recombination suppression and thus for linkage disequilibrium.
D000818:Animals; D007446:Chromosome Inversion; D002874:Chromosome Mapping; D004262:DNA Restriction Enzymes; D005802:Genes, MHC Class II; D008040:Genetic Linkage; D006183:H-2 Antigens / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics*; D011995:Recombination, Genetic
D006183:H-2 Antigens; D004262:DNA Restriction Enzymes