title: Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide.
abstract: The ability to taste the substance phenylthiocarbamide (PTC) has been widely used for genetic and anthropological studies, but genetic studies have produced conflicting results and demonstrated complex inheritance for this trait. We have identified a small region on chromosome 7q that shows strong linkage disequilibrium between single-nucleotide polymorphism (SNP) markers and PTC taste sensitivity in unrelated subjects. This region contains a single gene that encodes a member of the TAS2R bitter taste receptor family. We identified three coding SNPs giving rise to five haplotypes in this gene worldwide. These haplotypes completely explain the bimodal distribution of PTC taste sensitivity, thus accounting for the inheritance of the classically defined taste insensitivity and for 55 to 85% of the variance in PTC sensitivity. Distinct phenotypes were associated with specific haplotypes, which demonstrates that this gene has a direct influence on PTC taste sensitivity and that sequence variants at different sites interact with each other within the encoded gene product.
authors.affiliation: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850, USA.
authors.forename: Un-kyung
authors.initials: UK
authors.lastname: Kim
authors.forename: Eric
authors.initials: E
authors.lastname: Jorgenson
authors.forename: Hilary
authors.initials: H
authors.lastname: Coon
authors.forename: Mark
authors.initials: M
authors.lastname: Leppert
authors.forename: Neil
authors.initials: N
authors.lastname: Risch
authors.forename: Dennis
authors.initials: D
authors.lastname: Drayna
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D002427:Cebidae / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D003001:Cloning, Molecular; D019295:Computational Biology; D019143:Evolution, Molecular; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006579:Heterozygote; D015186:Hominidae / Q000235:genetics; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008252:Macaca fascicularis / Q000235:genetics; D008297:Male; D010670:Phenylthiourea; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D044469:Racial Groups / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled; D017422:Sequence Analysis, DNA; D013649:Taste / Q000235:genetics*; D013652:Taste Threshold; D000098706:Taste Receptors, Type 2
chemical_list: D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D010670:Phenylthiourea