Polymorphic olfactory receptor genes and HLA loci constitute extended haplotypes

Abstract

Olfactory receptor (OR) genes are often clustered and are known to be located on most human chromosomes. In the largest OR gene cluster so far analyzed and sequenced in any organism, we have identified 27 OR genes between HLA-F and HFE, of which so far 23 are located within about 650 kilobasepairs between HLA-F and RFP. Their products could be involved in the recognition of individual-specific, MHC-dependent odours and be tailored to perform this function. In this first systematic OR gene polymorphism study, twelve HLA-linked OR genes were analyzed on ten HLA-homozygous or — hemizygous cell lines with different HLA haplotypes. All potentially functional HLA-linked OR genes were found to exhibit polymorphism, although the degree differed considerably. The nucleotide changes within a given gene occur at defined positions, and may be part of putative transmembrane domains or occur at other residues. It has been possible so far to define 12 haplotypes for the HLAlinked OR genes on the 18 chromosomes 6 analyzed. The strong linkage disequilibrium, which is known to extend from HLA-A to HFE, is expected to conserve these extended HLA/OR haplotypes. If HLA and HLA-linked polymorphic OR genes also turn out to be functionally connected, a view supported by our finding of polymorphism of these OR genes, the entire region might be considered to constitute an extended gene complex which could, as we have already suggested, be designated “Immuno-Olfactory Supercomplex” (IOS).