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PMID: 17973576 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genetic elucidation of human hyperosmia to isovaleric acid.

PLoS biology ·Vol. 5 ·No. 11 ·2007-10-30 ·Pages e284

Menashe I, Abaffy T, Hasin Y, Goshen S, Yahalom V, Luetje CW, Lancet D

Abstract

The genetic basis of odorant-specific variations in human olfactory thresholds, and in particular of enhanced odorant sensitivity (hyperosmia), remains largely unknown. Olfactory receptor (OR) segregating pseudogenes, displaying both functional and nonfunctional alleles in humans, are excellent candidates to underlie these differences in olfactory sensitivity. To explore this hypothesis, we examined the association between olfactory detection threshold phenotypes of four odorants and segregating pseudogene genotypes of 43 ORs genome-wide. A strong association signal was observed between the single nucleotide polymorphism variants in OR11H7P and sensitivity to the odorant isovaleric acid. This association was largely due to the low frequency of homozygous pseudogenized genotype in individuals with specific hyperosmia to this odorant, implying a possible functional role of OR11H7P in isovaleric acid detection. This predicted receptor-ligand functional relationship was further verified using the Xenopus oocyte expression system, whereby the intact allele of OR11H7P exhibited a response to isovaleric acid. Notably, we also uncovered another mechanism affecting general olfactory acuity that manifested as a significant inter-odorant threshold concordance, resulting in an overrepresentation of individuals who were hyperosmic to several odorants. An involvement of polymorphisms in other downstream transduction genes is one possible explanation for this observation. Thus, human hyperosmia to isovaleric acid is a complex trait, contributed to by both receptor and other mechanisms in the olfactory signaling pathway.

MeSH Terms
Adolescent Adult Animals Female Gene Expression Genotype Hemiterpenes Humans Linear Models Male Middle Aged Pentanoic Acids Phenotype Polymorphism, Single Nucleotide Pseudogenes Receptors, Odorant/genetics Sensory Thresholds Smell/genetics Xenopus
Chemicals
Hemiterpenes Pentanoic Acids Receptors, Odorant isovaleric acid
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Menashe Idan
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Abaffy Tatjana
Hasin Yehudit
Goshen Sivan
Yahalom Vered
Luetje Charles W
Lancet Doron
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Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0050284
Published
2007-10-30
Pages
e284
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC2043052
Subset
IM
Grants
NIDCD NIH HHS · DC000298 · United States
NIDCD NIH HHS · F32 DC000298 · United States
NIDCD NIH HHS · R01 DC000298 · United States
NIMH NIH HHS · MH66038 · United States
NIMH NIH HHS · R01 MH066038 · United States
Corrections
CommentIn
PMID: 20076651
External Links
PubMed source DOI: 10.1371/journal.pbio.0050284 PMC Full Text View journal details
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