Identification and characterization of coding single-nucleotide polymorphisms within a human olfactory receptor gene cluster.

Single-nucleotide polymorphisms (SNPs) were studied in 15 olfactory receptor (OR) coding regions, one control region and two noncoding sequences all residing within a 412 kb OR gene cluster on human chromosome 17p13.3, as well as in other G-protein coupled receptors (GPCRs). A total of 26 SNPs were identified in ORs, 21 of which are coding SNPs (cSNPs). The mean nucleotide diversity of OR coding regions was 0.078% (ranging from 0 to 0.16%), which is about twice higher than that of other GPCRs, and similar to the nucleotide diversity levels of noncoding regions along the human genome. The high polymorphism level in the OR coding regions might be due to a weak positive selection pressure acting on the OR genes. In two cases, OR genes have been found to share the same cSNP. This could be explained by recent gene conversion events, which might be a part of a concerted evolution mechanism acting on the OR superfamily. Using the genotype data of 85 unrelated individuals in 15 SNPs, we found linkage disequilibrium (LD) between pairs of SNPs located on the centromeric part of the cluster. On the other hand, no LD was found between SNPs located on the telomeric part of the cluster, suggesting the presence of several hot-spots for recombination within this cluster. Thus, different regions of this gene cluster may have been subject to different recombination rates.