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 considerable knowledge of the content of the class I region. In an effort to further understand the nature of the five 6.7 family members previously mapped to this region of the genome, we have further analyzed the cross-reactive members of the family and have observed additional genomic instability within the HLA-A subregion. Such genomic variation may underscore the slower evolutionary rates of the HLA-A allelic family and the extended linkage disequilibrium of markers distal to this locus. 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 demonstrate limited, composite similarity to RAG2 and complement C4a gene sequences. A pancreas-specific transcript embedded in a 6.7 cross-reactive fragment was found distal to HLA-H and suggests that the fragments 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 possibility that the great apes have suffered a recent deletion event within this region following the emergence of Homo sapiens.
Pichon
L
L
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Venditti
C
C
Harris
J
J
Ten Elshof
A
A
Pinelli
M
M
Chorney
M
M
D000818:Animals; D002460:Cell Line; D005805:Genes, MHC Class I; D016678:Genome; D006801:Humans; D005810:Multigene Family; D011323:Primates