Six HLA-D region α-chain genes on human chromosome 6: Polymorphisms and associations of DCα-related sequences with DR types

Abstract

Analysis of cosmid clones containing genes related to the HLA-DRα chain calls for at least six HLA-D region α-chain coding sequences in man; namely, DRα, DCα, DXα (very closely related to DCα), SBα1, SBα2 (two closely linked genes on the same cosmid clones), and DZα. The first four genes have been described previously. SBα2 and DZα are recently identified genes, characterized by their unique and, from a limited study, nonpolymorphic bands when used as probes for human DNA on Southern blots. All of the genes are present in somatic cell hybrids containing a human X/6 translocation chromosome, and so they are all presumably in the HLA region. The polymorphisms in the region of the DCα and related DXα genes were studied with Southern blots of DNA from a set of mostly homozygous HLA-D-typing cell lines. With EcoRI, the band patterns for the DCα gene corresponded to the major cross-reactive HLA-DR serotypes associated with DC (namely MT1, -2, and -3) while the DXα band was invariant. Both genes were polymorphic with the enzyme TaqI. Within some DR types additional polymorphic variation was detected at the DNA level, implying the existence of subtypes. The pattern of polymorphisms for DCα, and to a lesser extent for DXα, suggests that these genes may play an important role in certain HLA-D associations with diseases.