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 associated with several diseases. The sequences were analyzed for coding potential and their relevance to disease associations were assessed with respect to the level of polymorphism. Analysis of sequences located approximately 25kb centromeric of HLA-B reveals the existence of fibroblast growth factor receptor related sequences. These sequences designated PERB1 (FGFR6) reveal 80% homology, at both nucleic acid and amino acid level, to the immunoglobulin domain 1 (Ig-1) of the human fibroblast growth factor receptor 3 (FGFR3) gene. Amino acid comparison of 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, FGFR2 or FGFR4. Genomic sequence analysis, however, reveals no consensus splice sites and indicates the existence of inframe premature stop codons in the putative coding sequences. The results suggest that these sequences may represent FGFR gene fragments existing within the central 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 PERB1 (FGFR6) may exist within or in close proximity to the MHC.
Leelayuwat
C
C
Centre for Molecular Immunology and Instrumentation, University of Western Australia, Perth.
Abraham
L J
LJ
Pinelli
M
M
Townend
D C
DC
Wilks
A F
AF
Dawkins
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics; D011148:Pongo pygmaeus / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D015235:HLA-B Antigens; D017468:Receptors, Fibroblast Growth Factor