Abstract
To date, little is known about the role of olfactory receptor (OR) genes on smell performance. Thanks to the availability of whole-genome sequencing data of 802 samples, we identified 41 knockout (KO) OR genes (i.e., carriers of Loss of Function variants) and evaluated their effect on odor discrimination in 218 Italian individuals through recursive partitioning analysis. Furthermore, we checked the expression of these genes in human and mouse tissues using publicly available data and the presence of organ-related diseases in human KO (HKO) individuals for OR expressed in non-olfactory tissues (Fisher test). The recursive partitioning analysis showed that age and the high number (burden) of OR-KO genes impact the worsening of odor discrimination (p-value < 0.05). Human expression data showed that 33/41 OR genes are expressed in the olfactory system (OS) and 27 in other tissues. Sixty putative mouse homologs of the 41 humans ORs have been identified, 58 of which are expressed in the OS and 37 in other tissues. No association between OR-KO individuals and pathologies has been detected. In conclusion, our work highlights the role of the burden of OR-KO genes in worse odor discrimination.
Highlights
Animals, including humans, perceive themselves and everything surrounding them thanks to their senses, and only the sensory coding allows species to make crucial decisions that lead to a specific behavioral response [1]
Several works have already highlighted the effect of variants in olfactory receptor (OR) genes on the perception of smell [23,24,25,26,27,28,29,30,31], but, to our knowledge, no studies evaluate the effect of the burden of Olfactory Receptor Knockout (OR-KO) genes on smell ability
Thanks to the availability of whole genome sequencing (WGS) of 802 Italian samples, we identified 41 OR-KO genes. We evaluated their effect on the smell capacity in 218 individuals, for whom the odor discrimination evaluation was assessed through the Sniffin’ Sticks test
Summary
Animals, including humans, perceive themselves and everything surrounding them thanks to their senses, and only the sensory coding allows species to make crucial decisions that lead to a specific behavioral response [1]. The number of OR genes and pseudogenes in the genome varies significantly between different species [7,8,9] It does not always correlate with their smell ability, suggesting that other factors may be involved (e.g., larger surfaces of OE in dogs, a high number of glomeruli in humans, etc.) [10,11,12]. An inter-individual phenotypic variation in the olfactory function within members of the same species suggests a different pattern of genetic variants in ORs and an influence of both environment and demographic factors [15,16,17]. More efforts are needed to increase our knowledge of the genetic basis of this sense In this light, the possibility of studying individuals defined as human knockout (HKO) (i.e., carriers of biallelic loss of function (LoF) variants) can give the unprecedented opportunity further to explore the role and the function of OR genes. We studied the expression pattern of the OR-KO genes in the OS and other tissues of both humans and mice and the possible development of organ-related diseases in individuals’ OR-KO for proteins expressed in the non-olfactory epithelium
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