title: The missense of smell: functional variability in the human odorant receptor repertoire.
abstract: 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.
authors: 1] Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA. [2] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA. [3] Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Joel D
authors: 0000000250564598
authors: JD
authors: Mainland
authors: Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, New York, USA.
authors: Andreas
authors: A
authors: Keller
authors: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA. [2].
authors: Yun R
authors: YR
authors: Li
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA.
authors: Ting
authors: T
authors: Zhou
authors: Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
authors: Casey
authors: C
authors: Trimmer
authors: Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA.
authors: Lindsey L
authors: LL
authors: Snyder
authors: 1] Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA. [2] Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors: Andrew H
authors: AH
authors: Moberly
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA.
authors: Kaylin A
authors: KA
authors: Adipietro
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA.
authors: Wen Ling L
authors: WL
authors: Liu
authors: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA. [2].
authors: Hanyi
authors: H
authors: Zhuang
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA.
authors: Senmiao
authors: S
authors: Zhan
authors: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA. [2].
authors: Somin S
authors: SS
authors: Lee
authors: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA.
authors: Abigail
authors: A
authors: Lin
authors: 1] Department of Molecular Genetics and Microbiology, Duke University Medical Center, Research Drive, Durham North Carolina, USA. [2] Department of Neurobiology and Duke Institute for Brain Sciences, Duke University Medical Center, Research Drive, Durham North Carolina, USA.
authors: Hiroaki
authors: H
authors: Matsunami
mesh_terms: D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006139:Guaiacol / Q000494:pharmacology; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009812:Odorants; D055696:Olfactory Perception / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011601:Psychophysics; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism*; D012903:Smell / Q000502:physiology*; D055815:Young Adult
chemical_list: D018035:Receptors, Odorant; D006139:Guaiacol