Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes.

Abstract

Three sets of cosmid clones, containing the HLA-DR.alpha. chain gene and 2 additional related genes, were isolated from human genomic DNA libraries by using a c[complementary]DNA probe for the HLA-DR.alpha. chain. Southern blot analysis using DNA from somatic cell hybrids indicated that all of the clones mapped to chromosome 6. Partial sequence analysis showed that the 2 additional related genes were highly homologous to each other, and to the HLA-DR.alpha. chain, in parts of the exon that encoded the .alpha.2 domain but were more divergent in intron sequences. One of the genes corresponds to the HLA-DR-related DC series. DNA probes made from this gene revealed marked restriction enzyme polymorphism when hybridized to genomic DNA from HLA-DR typed homozygous cell lines. The patterns obtained from a number of homozygous and heterozygous cell lines correlated with the HLA-DR crossreactive serotypes, and also indicated that there is a further sequence in the haploid human genome that is closely homologous with the DC.alpha. chain sequence. One family was studied and showed the expected HLA-DR-associated inheritance of restriction enzyme patterns. No polymorphism was yet demonstrated in restriction enzyme fragments that include the other cloned sequence, which may correspond to the SB.alpha. chain gene or to a novel HLA-DR-related gene. There are apparently at least 3 sequences in the human genome related, but not identical, to the HLA-DR.alpha. chain gene.