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RESEARCH PRODUCT

Towards a Physical Map of the HLA Complex

subject

description

The human major histocompatibility (HLA) complex is located on the short arm of chromosome 6 in the 6p21.31→6p21.33 region (1,2). There are three clusters of genes, the HLA class I, II, and III regions. Whereas the class III loci are only moderately polymorphic (see (3) for review), the class I and II genes which encode cell surface glycoproteins show an extreme degree of polymorphism. There are a minimum of 17 class I loci (4) and at least 15 genes for class II alpha and beta chains (5). In addition, we (6) and others (7) have recently demonstrated that also the loci for tumor necrosis factor (TNFA) and lymphotoxin (TNFB) are part of the HLA complex [see also Ragoussis et al., this volume]. A precise knowledge of the exact arrangement of HLA genes and the physical distances involved is essential for an understanding of several important properties of the HLA system, among them the association of haplotypes with diseases (8) and the phenomenon of linkage disequilibrium between alleles of different loci (9). Towards this end, we have assigned individual HLA genes to large DNA restriction fragments separated by pulsed field gel electrophoresis or related techniques. This allowed us to construct a molecular map of the HLA complex spanning at least 4000 kilobasepairs (kb).