Genetic basis of olfactory cognition: extremely high level of DNA sequence polymorphism in promoter regions of the human olfactory receptor genes revealed using the 1000 Genomes Project dataset

Abstract

The molecular mechanism of olfactory cognition is very complicated. Olfactory cognition is initiated by olfactory receptor proteins (odorant receptors), which are activated by olfactory stimuli (ligands). Olfactory receptors are the initial player in the signal transduction cascade producing a nerve impulse, which is transmitted to the brain. The sensitivity to a particular ligand depends on the expression level of multiple proteins involved in the process of olfactory cognition: olfactory receptor proteins, proteins that participate in signal transduction cascade, etc. The expression level of each gene is controlled by its regulatory regions, and especially, by the promoter [a region of DNA about 100–1000 base pairs long located upstream of the transcription start site (TSS)]. We analyzed single nucleotide polymorphisms using human whole-genome data from the 1000 Genomes Project and revealed an extremely high level of single nucleotide polymorphisms in promoter regions of olfactory receptor genes and HLA genes. We hypothesized that the high level of polymorphisms in olfactory receptor promoters was responsible for the diversity in regulatory mechanisms controlling the expression levels of olfactory receptor proteins. Such diversity of regulatory mechanisms may cause the great variability of olfactory cognition of numerous environmental olfactory stimuli perceived by human beings (air pollutants, human body odors, odors in culinary etc.). In turn, this variability may provide a wide range of emotional and behavioral reactions related to the vast variety of olfactory stimuli.

Critical Association Study of Olfactory Receptor Gene Polymorphism in Diabetic Complications

“…The study provided strong genetic confirmation for already existing reports about the unique appearance of OR that is inextricably related to immunological function [20][21][22]. In addition, it might be an interesting genetic reasoning for the accumulative evidence that OR dysfunction exists in brain diseases such as Multiple Sclerosis [23][24][25][26][27][28][29] OR14 gene is located in the telomeric region of HLA-F [14] where an interesting haplotype-specific association between T1D and a SNP in the promoter region of OR14 gene, rs9257691, has been reported [14].…”

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

“…The benefits of using the ontological and pathway analyses for functional annotation of group of genes revealed by different criteria have been considered in numerous publications [38, 61, 62]…”

I Smell a Rat!

“…Over time, OR clusters have been shuffled around the genome so that there are now about 50 locations scattered across most of our chromosomes (Fig. 2) …”

“…Even the same gene responds differently in different people . That also applies to the DNA sequences in the putative OR regulatory regions, the sequences of which are more variable in a sample of humans from different populations than are regulatory sequences near nonolfactory genes . This suggests that the amount, as well as the choice of ORs expressed in the cell may constitute subtle additional variation in sensitivity to that OR's potential binding targets.…”