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

• Published in: Nature (London) 1983-01, Vol.306 (5941), p.380-383
• Main Authors: Shin, Hee-Sup, Flaherty, Lorraine, Artzt, Karen, Bennett, Dorothea, Ravetch, Jeffrey
• Format: Article
• Language: English
• Subjects: Animals; Chromosome Inversion; Chromosome Mapping; DNA Restriction Enzymes; Genes, MHC Class II; Genetic Linkage; H-2 Antigens - genetics; Humanities and Social Sciences; letter; Mice; Mice, Mutant Strains - genetics; multidisciplinary; Recombination, Genetic; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/306380a0

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 1 . The observation of free recombination occurring between two complementary t -haplotypes suggested a chromosomal mismatch between t and normal chromosomes 2 . Recent data showing the H–2 complex to be misplaced relative to two other markers, T and tf , in t -haplotypes 3 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 4 . 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.