We have used the term supratype to describe combinations of alleles and have examined associations with disease. In RA and insulin-dependent diabetes one or more supratypes appear to be important but their functional significance remains obscure. In MG and SLE the HLA supratype may contain loci involved in immunoregulation, complement synthesis and hormone metabolism. MG induced by D-Pen is associated with Bw35/DR1 rather than A1, B8, DR3. In contrast there is no evidence of a supratype in AS. We have proposed a model for the pathogenesis of sacroiliitis and AS and have postulated two non-linked genes which act stepwise upon HLA-B27. There are cogent reasons for examining the functional effects of known loci within the MHC and particularly those involved in the expression of complement components.

The human MHC is located within ti2 cM of the 6p21.3 band (1) and contains at least 20 genes coding "inter alia" for three major classes of proteins : HLA A, B, and C (class I), HLA DP, DQ, and DR (class II), and serum complement components, C2, C4, and Bf. In addition, the region contains genes for 21-hydroxylase (210H) and TNF (2) . Thus, the MHC is a chromosomal segment containing several gene clusters of uncertain biological significance, but undoubtedly plays a role in disease susceptibility.The most striking feature of the MHC is the remarkable degree of polymorphism ; there are numerous alleles at multiple loci, including HLA A, B, DR, and C4 . Surprisingly, however, some 70% of Caucasoids possess 1 or 2 of only 20 particular sets of MHC alleles (3) variously referred to as supratypes (4), extended haplotypes (5), or preferential allelic associations (6) . Each of these supratypes has its own specific disease associations (4) . Since we have shown that supratypes define and mark entire chromosomal segments of some 2 megabases (Mb),' we postulated that each supratype would contain its own unique set of new genes, deletions, duplications, and insertions (7) . Furthermore, at least some of these supratype-specific arrangements (7) may be relevant to function and disease .The technique of pulsed field gel electrophoresis (PFGE) allows separation of DNA molecules of up to 2 Mb in size (8) . Using restriction endonucleases that cut infrequently, long range maps have been produced (7, 9-12), but there are discrepancies .Most of these maps (9-12) can only be approximations, since the importance of supratype-specific patterns was not appreciated . Accordingly, we present here the PFGE profiles of six different MHC supratypes and provide evidence for extensive deletions and insertions . These changes are present in unrelated subjects with the same supratype and are therefore predictable from comprehensive allotyping of the products of the known genes within the HLA B to DQ region .

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