STUDIES OF THE 6.7-FAMILY OF DISPERSED GENOMIC FRAGMENTS WITHIN THE MHC CLASS-I REGION

Searches for MHC-encoded disease susceptibility genes have led to cons iderable knowledge of the content of the class I region. In an effort to further understand the nature of the five 6.7 family members previo usly mapped to this region of the genome, we have further analyzed the cross-reactive members of the family and have observed additional gen omic instability within the HLA-A subregion. Such genomic variation ma y underscore the slower evolutionary rates of the HLA-A allelic family and the extended linkage disequilibrium of markers distal to this loc us. Moreover, one of the largest genes associated with a member of the 6.7 family, the 3.8-1 gene found proximal to HLA-B, was found to demo nstrate limited, composite similarity to RAG2 and complement C4a gene sequences. A pancreas-specific transcript embedded in a 6.7 cross-reac tive fragment was found distal to HLA-H and suggests that the fragment s have remained linked to transcriptionally active chromatin comprised of both a major class I gene and a second novel coding sequence since the time of their dispersal. The absence of a 6.7 fragment in the HLA -B subregions of higher nonhuman primates lends credence to the possib ility that the great apes have suffered a recent deletion event within this region following the emergence of Homo sapiens.