THE PRIMATE MHC CONTAINS SEQUENCES RELATED TO THE FIBROBLAST GROWTH-FACTOR RECEPTOR GENE FAMILY

We have cloned and sequenced a genomic region centromeric of the HLA-B locus from different MHC ancestral haplotypes. These haplotypes are a ssociated with several diseases. The sequences were analyzed for codin g potential and their relevance to disease associations were assessed with respect to the level of polymorphism. Analysis of sequences locat ed approximately 25kb centromeric of HLA-B reveals the existence of fi broblast growth factor receptor related sequences. These sequences des ignated PERB1 (FGFR6) reveal 80% homology, at both nucleic acid and am ino acid level, to the immunoglobulin domain 1 (Ig-1) of the human fib roblast growth factor receptor 3 (FGFR3) gene. Amino acid comparison o f the Ig-1 domain of PERB1 to those of other FGFR molecules indicates that PERB1 is more closely related to FGFR3 and FGFR5 than to FGFR1, F GFR2 or FGFR4. Genomic sequence analysis, however, reveals no consensu s splice sites and indicates the existence of inframe premature stop c odons in the putative coding sequences. The results suggest that these sequences may represent FGFR gene fragments existing within the centr al MHC. Sequence analysis of the Mhc in 6 chimpanzee and one orangutan indicates that the existence of PERB1 predates the speciation of the three species. The fact that the MHC contains a mixture of functional and nonfunctional (pseudo) genes suggests that a functional copy of PE RB1 (FGFR6) may exist within or in close proximity to the MHC.