The impact of the discovery of the variable human sensitivity to phenylthiocarbamide on the understa

It has the unusual property that it either tastes very bitter or is virtually tasteless, depending on the genetic makeup of the taster. The ability to taste PTC is often treated as a dominant genetic trait, although inheritance and expression of this trait are somewhat more complex. A nearby colleague complained about the bitter taste, while Fox, who was closer and should have received a strong dose, tasted nothing. Fox then continued to test the taste buds of assorted family and friends, setting the groundwork for future genetic studies.

Advanced Search Abstract Mutational polymorphism in the TAS2R38 bitter taste receptor is a key determinant of threshold taste detection of isolated compounds, such as phenylthiocarbamide PTC and propylthiouracil PROPas well as complex orosensation-mediated traits such as diet choice and smoking habits.

However, TAS2R38 harbors extensive additional polymorphism whose functional significance remains unknown. To examine this variation, we ascertained genetic diversity in 56 Caucasian subjects via whole-gene sequencing, analyzed allele-specific responses to 5 TAS2R38 agonists PTC, PROP, goitrin, methimazole, and sinigrin using in vitro assays, and assessed genotypic associations with threshold detection phenotypes.

Haplotypes other than PAV and AVI did not exhibit phenotypic associations in our sample, possibly as a result of their low frequencies.

However, prior studies have indicated that these alleles are common in some global regions, suggesting that alleles rare in our sample may be phenotypically relevant in other populations. By shaping the attractiveness of food and other substances such as cigarette smoke before they are even ingested, it is powerfully positioned to influence intake Duffy This has long suggested that variation in sensitivity could translate into both immediate preferences and long-term downstream effects, a hypothesis borne out in multiple reports of association between bitter responses and traits including food and alcohol choices, smoking habits, susceptibility to colon polyps, thyroid function, and body mass index Drewnowski and Rock ; Duffy and Bartoshuk ; Enoch et al.

Thus, dissecting the mechanisms underlying variability in perception is a potentially powerful means of identifying the origins of individual and group differences in both consumption and susceptibility. Numerous complex factors including age, sex, morphology, and environment interact to produce major differences in bitter perception among individuals Bartoshuk and Beauchamp However, mounting evidence indicates that mutations in TAS2R receptors, a family of 25 cell-surface G protein—coupled receptors expressed in taste buds, make particularly important contributions Drayna TAS2Rs, which control the earliest stages of bitter taste transduction, harbor extensive genetic polymorphism including numerous amino acid replacements likely to affect function Kim et al.

Studies of genetic and functional diversity in 5 receptor genes, TAS2R9,andhave isolated alleles exhibiting divergent functionality that interact to shape taste responses to artificial sweeteners such as acesulfame K and saccharin, phytotoxins such as aloin, amygdalin, aristolochic acid, and goitrin, and a range of pharmaceuticals Kim et al.

By detecting the origins of variance in response to specific agonists, these studies have identified candidate sources of variance in related endpoint phenotypes such as preferences for artificial sweeteners and vegetables Dinehart et al.

TAS2R38, which mediates taste responses to thioamides including the classic markers PTC and PROP, is the most intensively investigated bitter receptor in the context of both functional and epidemiological associations.

Subsequent investigation revealed that these alleles also associate with long-term trends in tobacco use, food preferences, and obesity Cannon et al. Thus, TAS2R38 has been strongly implicated in connections between taste, behavior, and fitness.

Introduction

However, recent studies have revealed that TAS2R38 harbors extensive genetic variation beyond the PAV and AVI alleles, with 19 amino acid variants cataloged to date in worldwide populations, which could underlie unrecognized functional and phenotypic diversity Wooding et al.

In this study, we sought to better define the functional and phenotypic underpinnings of TAS2Rmediated bitter responses by comprehensively examining a cohort of 56 Caucasian subjects using whole-gene sequencing, dose—response analyses of discovered haplotypes, and tests for association with threshold taste responses to thioamides and other compounds.

Following initial recruitment, participants providing informed consent were screened via self-report to identify individuals with prior clinically diagnosed taste deficits or other significant health problems. Candidates meeting selection criteria were invited to take part in 6 taste tests and a blood draw for DNA extraction and genetic analysis.

Twenty-eight subjects were participants in an earlier study of goitrin perception in the laboratory of SPW Wooding et al. Taste phenotypes Detection threshold measures were used to examine taste responses to 6 compounds potentially informative about phenotypic variation and functional polymorphism in TAS2R Phenotypes were assessed using the blind sorting method of Harris and Kalmuswhich estimates the lowest concentration at which a subject can distinguish tastant and control solutions in a stepwise dilution series, or perception threshold.variation in taste sensitivity and goes back to Fox’s discovery in that there is a universal bipolar distribution of individuals based on their sensitivity to the bitter taste of the chemical compound PTC.

Perspectives Anecdotal, Historical and Critical Commentaries on Genetics Edited by James F.

Crow and William F. Dove Phenylthiocarbamide: A Year Adventure in Genetics and Natural Selection Stephen Wooding1 Department of Human Genetics, University of Utah, Salt Lake City, Utah V ARIATION in taste sensitivity to the bitter com-.

Mutational polymorphism in the TAS2R38 bitter taste receptor is a key determinant of threshold taste detection of isolated compounds, such as phenylthiocarbamide (PTC) and propylthiouracil (PROP), as well as complex orosensation-mediated traits such as diet choice and smoking habits.

As sensitivity to bitter taste (phenylthiocarbamide [PTC] perception) has been maintained at high frequency worldwide, its use as a potential genetic marker for food preferences and dietary. Facsimile of the heading and first paragraph of Arthur Fox's first article on PTC sensitivity in the Proceedings of the National Academy of Sciences (Fox ).

Just as the discovery of variable PTC sensitivity by Fox opened the door for Fisher, Ford, and Huxley to take early steps toward understanding the evolutionary origins of genetic variation, the recent discovery of dozens more such genes has opened many such doors (K im et al.

; S oranzo et al. ).