Genetic elucidation of human hyperosmia to isovaleric acid.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Menashe, I; Abaffy, T; Hasin, Y; Goshen, S; Yahalom, V; Luetje, CW; Lancet, D
Published Date
- October 30, 2007
Published In
Volume / Issue
- 5 / 11
Start / End Page
- e284 -
PubMed ID
- 17973576
Pubmed Central ID
- PMC2043052
Electronic International Standard Serial Number (EISSN)
- 1545-7885
Digital Object Identifier (DOI)
- 10.1371/journal.pbio.0050284
Language
- eng
Conference Location
- United States