The missense of smell: functional variability in the human odorant receptor repertoire.

Mainland, Joel D; Keller, Andreas; Li, Yun R; Zhou, Ting; Trimmer, Casey; Snyder, Lindsey L; Moberly, Andrew H; Adipietro, Kaylin A; Liu, Wen Ling L; Zhuang, Hanyi; Zhan, Senmiao; Lee, Somin S; Lin, Abigail; Matsunami, Hiroaki

The missense of smell: functional variability in the human odorant receptor repertoire.

dc.contributor.author	Mainland, Joel D
dc.contributor.author	Keller, Andreas
dc.contributor.author	Li, Yun R
dc.contributor.author	Zhou, Ting
dc.contributor.author	Trimmer, Casey
dc.contributor.author	Snyder, Lindsey L
dc.contributor.author	Moberly, Andrew H
dc.contributor.author	Adipietro, Kaylin A
dc.contributor.author	Liu, Wen Ling L
dc.contributor.author	Zhuang, Hanyi
dc.contributor.author	Zhan, Senmiao
dc.contributor.author	Lee, Somin S
dc.contributor.author	Lin, Abigail
dc.contributor.author	Matsunami, Hiroaki
dc.coverage.spatial	United States
dc.date.accessioned	2013-12-18T16:40:15Z
dc.date.issued	2014-01
dc.description.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.
dc.identifier	http://www.ncbi.nlm.nih.gov/pubmed/24316890
dc.identifier	nn.3598
dc.identifier.eissn	1546-1726
dc.identifier.uri	https://hdl.handle.net/10161/8268
dc.language	eng
dc.publisher	Springer Science and Business Media LLC
dc.relation.ispartof	Nat Neurosci
dc.relation.isversionof	10.1038/nn.3598
dc.subject	Adult
dc.subject	Aged
dc.subject	Dose-Response Relationship, Drug
dc.subject	Female
dc.subject	Gene Frequency
dc.subject	Genetic Variation
dc.subject	Genotype
dc.subject	Guaiacol
dc.subject	Humans
dc.subject	Linear Models
dc.subject	Male
dc.subject	Middle Aged
dc.subject	Odorants
dc.subject	Olfactory Perception
dc.subject	Polymorphism, Single Nucleotide
dc.subject	Psychophysics
dc.subject	Receptors, Odorant
dc.subject	Smell
dc.subject	Young Adult
dc.title	The missense of smell: functional variability in the human odorant receptor repertoire.
dc.type	Journal article
duke.contributor.orcid	Matsunami, Hiroaki\|0000-0002-8850-2608
pubs.author-url	http://www.ncbi.nlm.nih.gov/pubmed/24316890
pubs.begin-page	114
pubs.end-page	120
pubs.issue	1
pubs.organisational-group	Basic Science Departments
pubs.organisational-group	Duke
pubs.organisational-group	Duke Cancer Institute
pubs.organisational-group	Duke Institute for Brain Sciences
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Institutes and Provost's Academic Units
pubs.organisational-group	Molecular Genetics and Microbiology
pubs.organisational-group	Neurobiology
pubs.organisational-group	School of Medicine
pubs.organisational-group	University Institutes and Centers
pubs.publication-status	Published
pubs.volume	17

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