| dc.description.abstract | The human olfactory system has enormous discriminatory power, with the ability to detect millions
of different odorants. The initial recognition of chemical volatiles is performed by the large family
of seven-transmembrane (7-TM) olfactory receptors (ORs), expressed in the olfactory neurons.
This multigene family with approximately four hundred functional genes in humans, contribute
essentially to detect and discriminate an extraordinary range of odors. Interestingly, human
olfactory sensitivity also differs between individuals and populations. This feature has been
related in some cases to genetic variation among individuals, thus the contribution of the
genotype plays an important role in the perceptual variations for a given odor. Despite the
extensive information about human olfactory thresholds for hundreds of chemical volatiles,
studies on the genotype-phenotype associations of ORs natural variants have been limited to a
few examples. Here, we analyzed a large compendium of more than sixty-five thousand natural
variants in the coding region of human OR genes available in the public database. To rationalize
this data, a topological assignation of the collected variants was conducted according to the
structural and functional knowledge of close related G-Protein coupled receptors (GPCRs). Our
results suggest that missense natural variants occur extensively within the OR family, especially
in the 7-TM domains. Interestingly, some of high frequency variations were located in conserved
functional regions, which could imply the disruption of the receptor activity. Finally, a web
application was developed to facilitate the public access and analysis of this information. The
human Olfactory Receptor Variant Database ( https://ramoncierco.shinyapps.io/orvdb/) is a free
online resource, which presents a complete compendium of 65.975 SNVs in 361 human OR
genes and several tools for evaluate their localization and impact on the receptor structure and
function. | es |
