Inversion in the H–2 complex of t-haplotypes in mice

Abstract

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 chromosomes¹. The observation of free recombination occurring between two complementary t-haplotypes suggested a chromosomal mismatch between t and normal chromosomes². Recent data showing the H–2 complex to be misplaced relative to two other markers, T and tf, in t-haplotypes³ 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-haplotypes⁴. 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_α 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.