February 21, 2003 — The ability to discern bitter tastes-from acrid nicotine smoke to sauerkraut-can be traced to a gene discovered by researchers at the University of Utah, National Institutes of Health (NIH), and Stanford University.

The discovery, described in the Feb. 21 issue of the journal Science, confirms the importance of the role played by healthy, large multi-generation families in genetic studies, according to Mark F. Leppert, Ph.D., professor and co-chair of the U of U School of Medicine Department of Human Genetics.

“This study demonstrates the power of large reference families to reveal the genetic basis of complex human traits,” Leppert said.

Leppert, along with Hilary H. Coon, Ph.D., U research associate professor of psychiatry, worked on the project with Dennis Drayna, Ph.D., and Un-kyung Kim, Ph.D., both of the NIH, and Neil Risch, Ph.D., of Stanford.

The ability to taste, which is dominantly inherited, is one of the most studied of human traits. Researchers for decades have used a compound called phenylthiocarbamide (PTC) to test people’s ability to taste. Studies have shown that 70 percent of the U.S. population tastes PTC from mildly to intensely bitter, while the remaining 30 percent cannot taste it all.

The ability to taste PTC affects dietary choices, according to some studies. Other investigations have suggested that people who cannot taste PTC may not experience the bitter taste of nicotine, which could lead to prolonged smoking.

To find the gene that allows people to taste bitter flavors, researchers from the U of U and NIH started testing Utah families in 1997 for their ability to taste PTC. This study, called the Utah Genetic Reference Project, eventually included 36 multi-generational Utah families. This project is funded by the Wm. Keck foundation of Los Angeles.

After testing about 25 families, the researchers identified those people who could not taste PTC. Using a technique called genetic linkage, the researchers then identified a small region on human chromsome 7 that in all likelihood contained the gene for PTC taste. (Results of this study will be published in the scientific literature soon, according to Leppert.)

Once this chromosomal region was identified, additional variations in the DNA within the region, called single nucleotide polymorphisms (SNPs), were learned. Using these new SNP variations the Utah and NIH researchers then identified an even smaller region on chromosome 7 that shows a linkage imbalance between SNP markers and the ability to taste PTC.

In this limited region where the SNP imbalance occurred, the researchers found the gene that allows people to taste PTC. They also discovered that the PTC gene encodes a member of the bitter taste receptor family, TAS2R.

Three SNPs give rise to five forms of the PTC gene worldwide and explain the distribution of taste sensitivity among unrelated people, according to the researchers. One of the gene forms prevents people from tasting PTC at all. The remaining forms are associated with varying degrees of ability to taste PTC.

People who cannot taste PTC, whether they are European or Asian, are descended from a common ancestor in prehistoric Africa, the researchers said.

Discovery of the gene is an example of how basic science launches new ways to think about human behavior, said the director of the National Institute on Deafness and Other Communication Disorders, a branch of the NIH that supported the study.

“This research promises to open a pathway to better understanding about what drives certain human behaviors, including those associated with smoking and eating,” said James F. Battey, Jr., M.D., Ph.D. “It is this kind of collaboration and focused effort that will yield far-reaching benefit.”