Variation and linkage disequilibrium within odorant receptor gene clusters linked to the human major...

Odorant receptors (OR) are G-protein-coupled receptors that are predominantly expressed in the membrane of olfactory neurons. Members of the two OR gene clusters on the short arm of human chromosome 6 could be involved in major histocompatibility complex (MHC)-associated behavioral traits, such as olfaction-influenced mate selection and cryptic female choice. In this context, OR gene polymorphisms and haplotypes are likely to play an important role. Here we report an investigation of polymorphisms within 12 MHC-linked OR genes in 10 human cell lines. Eight of these OR loci belong to the telomeric, smaller OR gene cluster, whereas four are located centromeric, between the first cluster and the MHC. We also assessed part of this genomic region using sequence data from eight additional cell lines that had previously been sequenced. Thirteen novel OR variants were found through direct DNA sequencing and cloning, in addition to the detection of OR polymorphisms already known, and the number of OR cluster haplotypes could be increased to 21. Two loci belonging to the telomeric cluster (OR2B8P and OR1F12) were found to exhibit nonfunctional and potentially functional alleles and should therefore be considered as segregating pseudogenes. The results provide a detailed picture regarding polymorphisms and phenotypic variation in an ethnically diverse sample of major histocompatibility complex-linked OR clusters and identify a subregion of unusually pronounced genetic variability. We expand these data by analyzing linkage disequilibrium both within these OR clusters as well as between them and the HLA complex in 11 unrelated HapMap populations. The sequence data described in this paper have been submitted to the GenBank database under the accession numbers GU251059, GU251060, GU251061, GU251062, GU251063, GU251064, GU251065, GU251066, GU251067, GU251068, GU251069, GU251070, GU251071, and GU251072.