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Scientist identify gene that determines bimodal distribution of taste sensitivity
Maryland | Friday, February 21, 2003, 08:00 Hrs  [IST]

Scientists have identified the gene that determines the ability to distinguish a wide class of bitter tastes. How individuals are genetically predisposed to respond or not respond to the bitter taste of substances like nicotine and certain foods may have broad implications for nutritional status and tobacco use. The research was done in a collaboration between the National Institutes of Health, the University of Utah and Stanford University for the first time.

By estimates, more than 10 million American students have been offered "taste" testing to identify their ability to recognize or discriminate bitter taste and to introduce them to inherited traits. In more formal research, anthropologists have tested people around the world, over decades, for this same ability or inability to experience bitter taste.

Why are some people "tasters" and others "non-tasters" and why is it important? The ability to taste, tested using a compound phenylthiocarbamide (PTC), is one of the best studied inherited traits in humans. Studies over the past 70 years, have demonstrated that taste variation is common in the U.S. population: about 30 per cent of the population are PTC (a prototype of a class of bitter substances) non-tasters, while 70 per cent are tasters of PTC, experiencing it as intensely bitter. The ability to taste PTC has been known to be dominantly inherited.

Previous studies had demonstrated that PTC status affects dietary choices. Other earlier investigation suggests that non-tasters may not experience the bitter taste of nicotine in cigarettes and may be at greater risk for prolonged smoking.

Dennis Drayna, National Institute on Deafness and Other Communication Disorders, NIH, project leader of the collaboration, explained, "We have identified a gene on chromosome 7 that exists in five different forms throughout the world. One of these forms confers a severe deficit in taste ability, while the other forms produce intermediate to fully sensitive taste abilities. This gene codes for part of the bitter taste receptor complex which exists in cells on the tongue. A study with this breadth could not have been done without outstanding collaboration," said Drayna. Drayna conducted all the taste testing of subjects in this study. His NIDCD collaborator, Un-kyung Kim, performed molecular biological studies and gene identification studies.

At Stanford University, Neil Risch provided a powerful statistical analytic strategy and Eric Jorgenson lent his expertise in the analysis of quantitative traits. Mark Leppert a key collaborator at the University of Utah, directs the W.M. Keck Foundation/University of Utah Genetic Reference Project (UGRP) project, which assembles significant data about large Utah families. These families have been extensively genetically analyzed in the past, and this data includes the results of extensive medical testing and evaluation of family members and creates genetic informational databases.

Using information from a variety of populations and individuals with differences in their ability to sense PTC, these investigators identified the small region on 7q that shows strong linkage disequilibrium between SNP markers (single nucleotide polymorphisms), and PTC sensitivity in unrelated subjects gathered at the NIH. SNPs are the DNA sequence variations that occur when a single nucleotide (A,T,C,or G) in the genome sequence is altered. The region on 7 q contains a single gene, the investigators are calling PTC, that encodes a member of the known TAS2R bitter taste receptor family.

The investigators have dramatically demonstrated that the linkage disequilibrium between SNP markers and taster status exists across unrelated individuals from across the world. Those millions of Europeans, Asians, and individuals from other populations around the world who are non-tasters descended from a common ancestor who emerged from Africa far back in prehistory.

Human DNA sequences are overwhelmingly similar, with some small, but sometimes important differences. For example, variations in DNA sequence can have a major impact on how humans respond to disease or to factors that effect health, such as food or tobacco. SNP analysis is an extremely powerful tool for use in population studies, because SNPs tend to be stable across time.

These scientists identified three coding SNPs giving rise to 5 forms of the gene worldwide. These differing forms of the gene completely explain the bimodal (taster vs. non-tasters) distribution of taste sensitivity. This accounts for the inheritance of what has been called genetic "taste insensitivity," and also explains 55-85 per cent of the overall variance in PTC sensitivity. Taster status was associated with specific forms of the gene, demonstrating the direct influence of this gene on PTC taste sensitivity, and, further, that variant sites interact with one another within the encoded gene product.

"This research promises to open a pathway to better understanding about what drives certain human behaviors including those associated with smoking and eating. It is this kind of collaboration and focused effort that will yield far-reaching benefit. This is how basic science launches new ways to think about human behavior and its foundations," said James F. Battey, Jr., Director of the National Institute on Deafness and Other Communication Disorders.

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