A new polymorphic and multicopy MHC gene family related to nonmammalian class I

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Abstract
We have used genomic analysis to characterize a region of the central major histocompatibility complex (MHC) spanning ∼ 300 kilobases (kb) betweenTNF andHLA-B. This region has been suggested to carry genetic factors relevant to the development of autoimmune diseases such as myasthenia gravis (MG) and insulin dependent diabetes mellitus (IDDM). Genomic sequence was analyzed for coding potential, using two neural network programs, GRAIL and GeneParser. A genomic probe, JAB, containing putative coding sequences (PERB11) located 60 kb centromeric ofHLA-B, was used for northern analysis of human tissues. Multiple transcripts were detected. Southern analysis of genomic DNA and overlapping YAC clones, covering the region fromBAT1 toHLA-F, indicated that there are at least five copies of PERB11, four of which are located within this region of the MHC. The partial cDNA sequence ofPERB11 was obtained from poly-A RNA derived from skeletal muscle. The putative amino acid sequence ofPERB11 shares ∼ 30%o identity to MHC class I molecules from various species, including reptiles, chickens, and frogs, as well as to other MHC class I-like molecules, such as the IgG FeR of the mouse and rat and the human Zn-α2-glycoprotein. From direct comparison of amino acid sequences, it is concluded thatPERB11 is a distinct molecule more closely related to nonmammalian than known mammalian MHC class I molecules. Genomic sequence analysis ofPERB11 from five MHC ancestral haplotypes (AH) indicated that the gene is polymorphic at both DNA and protein level. The results suggest thet we have identified a novel polymorphic gene family with multiple copies within the MHC.