The missense of smell: functional variability in the human odorant receptor repertoire.
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Humans have ~400 intact odorant receptors, but each individual has a unique set of genetic variations that lead to variation in olfactory perception. We used a heterologous assay to determine how often genetic polymorphisms in odorant receptors alter receptor function. We identified agonists for 18 odorant receptors and found that 63% of the odorant receptors we examined had polymorphisms that altered in vitro function. On average, two individuals have functional differences at over 30% of their odorant receptor alleles. To show that these in vitro results are relevant to olfactory perception, we verified that variations in OR10G4 genotype explain over 15% of the observed variation in perceived intensity and over 10% of the observed variation in perceived valence for the high-affinity in vitro agonist guaiacol but do not explain phenotype variation for the lower-affinity agonists vanillin and ethyl vanillin.
Dose-Response Relationship, Drug
Polymorphism, Single Nucleotide
Published Version (Please cite this version)10.1038/nn.3598
Publication InfoMainland, Joel D; Keller, Andreas; Li, Yun R; Zhou, Ting; Trimmer, Casey; Snyder, Lindsey L; ... Matsunami, Hiroaki (2014). The missense of smell: functional variability in the human odorant receptor repertoire. Nat Neurosci, 17(1). pp. 114-120. 10.1038/nn.3598. Retrieved from https://hdl.handle.net/10161/8268.
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Professor of Molecular Genetics and Microbiology
We are interested in the molecular mechanisms underlying chemosensation (taste and smell) in mammals. The receptors that detect odorants, pheromones, and many tastants including bitter and sweet chemicals are G-protein coupled receptors (GPCRs), which typically have seven transmembrane domains. There are many important questions that are still unanswered in chemosensory neurobiology. How do tens of thousands of different chemicals (tastants, odorants, or pheromones) interact with more than