Molecular organization of the D-Qa region of t-haplotypes suggests that recombination is an important mechanism for generating genetic diversity of the major histocompatibility complex.

We have determined the molecular maps of the H-2D and Qa regions of the t-complex haplotypes t12 and tw5 by chromosomal walking. Analysis with class I probes and other probes unique to the H-2D:Qa subregion indicates that the class I gene organization of t12 is: D1-D2-Q1-Q2-Q3-Qx-Q4-Q5-Q10, while that of tw5 is: D1-D2-Q1-Q2-Q4-Q5-Q10. Thus, the absence of the Q6-Q9 genes suggested previously in t-haplotypes was confirmed. A comparison of the molecular maps of the t12 and tw5 chromosomes revealed an extremely mosaic pattern of diversity: The regions between D1 and D2, and between Q4 and Q10, are very similar in both chromosomes. However, their Q1 to Q3 regions are strikingly different. Further comparisons of wild-type chromosomes and additional t-haplotypes by molecular mapping and genomic Southern blot hybridization with probes to the Q1-Q3 region showed a high level of polymorphism among both wild-type chromosomes and among t-haplotypes. The characteristics of the polymorphisms suggest that recombination may play an important role in generating this genetic diversity. Furthermore, recombination between wild-type and t-haplotype chromosomes may be involved.