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Science 299 (5610): 1221-1225

Copyright © 2003 by the American Association for the Advancement of Science

Positional Cloning of the Human Quantitative Trait Locus Underlying Taste Sensitivity to Phenylthiocarbamide

Un-kyung Kim,1 Eric Jorgenson,2 Hilary Coon,34 Mark Leppert,3 Neil Risch,25 Dennis Drayna1*

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.

1 National Institute on Deafness and Other Communication Disorders, National Institutes of Health, 5 Research Court, Rockville, MD 20850, USA.
2 Department of Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
3 Department of Human Genetics, University of Utah Medical Center, 15 North 2030 East, Salt Lake City, UT 84112, USA.
4 Department of Psychiatry, University of Utah Medical Center, Red Butte Health Center, 546 Chipeta Way, Salt Lake City, UT 84112, USA.
5 Division of Research, Kaiser Permanente, Oakland, CA 94612, USA.
*   To whom correspondence should be addressed. E-mail: drayna{at}nidcd.nih.gov



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