Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide

Science. 2003 Feb 21;299(5610):1221-5. doi: 10.1126/science.1080190.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Amino Acid Substitution
  • Animals
  • Cebidae / genetics
  • Chromosomes, Human, Pair 7 / genetics
  • Cloning, Molecular
  • Computational Biology
  • Continental Population Groups / genetics
  • Evolution, Molecular
  • Female
  • Genetic Linkage
  • Haplotypes
  • Heterozygote
  • Hominidae / genetics
  • Homozygote
  • Humans
  • Linkage Disequilibrium
  • Macaca fascicularis / genetics
  • Male
  • Phenylthiourea*
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / physiology
  • Receptors, G-Protein-Coupled
  • Sequence Analysis, DNA
  • Taste / genetics*
  • Taste Threshold

Substances

  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • taste receptors, type 2
  • Phenylthiourea