The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Bruce I. Turetsky - One of the best experts on this subject based on the ideXlab platform.
-
Phenylthiocarbamide ptc perception in ultra high risk for psychosis participants who develop schizophrenia testing the evidence for an endophenotypic marker
Psychiatry Research-neuroimaging, 2012Co-Authors: Warrick J Brewer, Paul J. Moberg, Ashleigh Lin, Gregory Smutzer, Barnaby Nelson, Alison R Yung, Christos Pantelis, Patrick D Mcgorry, Bruce I. TuretskyAbstract:Reports suggesting that schizophrenia participants are more likely to be Phenylthiocarbamide (PTC) non-tasters when compared to controls have recently been controversial. If supported, a genetic-based phenotypic variation in PTC taster status is implicated, suggesting a greater illness risk for those participants with recessive alleles for the TAS2R38 receptor. Should PTC insensitivity be a schizophrenia endophenotype, then it would be expected in follow-up of ultra high-risk for psychosis participants who later develop schizophrenia (UHR-S). UHR-S was hypothesised to show reduced PTC sensitivity compared to those who were previously at risk, but did not transition (UHR-NP). PTC perception was assessed in 219 UHR participants at long-term follow-up, of whom 53 had transitioned to psychosis (UHR-P) during the follow-up period. Fifteen of the 219 participants were diagnosed with schizophrenia. Seventy-eight had a family history of psychotic disorder. No differences in PTC taster status were found in UHR participants based upon transition to psychosis status, schizophrenia diagnosis, or family history of schizophrenia. This report indicates that schizophrenia development among UHR participants is not associated with PTC tasting deficits and fails to support previous findings that inability to detect the bitter taste of PTC is a schizophrenia endophenotype.
-
Association of schizophrenia with the Phenylthiocarbamide taste receptor haplotype on chromosome 7q.
Psychiatric genetics, 2012Co-Authors: Paul J. Moberg, Stephen J. Kanes, Raquel E. Gur, Vidyulata Kamath, Bruce I. TuretskyAbstract:Phenylthiocarbamide (PTC) taste sensitivity is an inherited trait determined primarily by allelic variation of the taste-receptor gene TAS2R38 on chromosome 7q. Results of prior studies examining the ability to taste PTC in patients with schizophrenia have been mixed because of the difficulties in measuring PTC taste sensitivity behaviorally. In the current study, we examined the TAS2R38 genotypes of schizophrenia patients to determine whether the increased prevalence of nontasters in this patient population was indicative of a specific genetic association. Our a-priori hypothesis was that schizophrenia patients would show an increased prevalence of the nontaster phenotype compared with controls. The genotypes of two nonsynonymous coding single-nucleotide polymorphisms in TAS2R38 were assayed for 176 schizophrenia patients and 229 healthy control individuals, and the two-allele haplotypes were estimated. There was an over-representation of the major PTC nontaster haplotype among patients of European descent, relative to control individuals of similar ancestry. Patients and controls of African ancestry did not differ. The PTC nontaster haplotype is a genetic marker that may be used to identify subsets of schizophrenia patients who potentially harbor vulnerability genes in this region of chromosome 7q.
-
Phenylthiocarbamide ptc perception in patients with schizophrenia and first degree family members relationship to clinical symptomatology and psychophysical olfactory performance
Schizophrenia Research, 2007Co-Authors: Paul J. Moberg, Stephen J. Kanes, Catherine C Balderston, David R Roalf, Colleen Mcgue, Christian G Kohler, Bruce I. TuretskyAbstract:The inability to taste Phenylthiocarbamide (PTC; “taste-blindness”) has been associated with a number of medical and neurological illnesses not typically related to taste. We examined PTC sensitivity in 67 schizophrenia patients, 30 healthy controls, and 30 first-degree relatives to determine whether taster status could represent a simple vulnerability marker. A higher prevalence of non-tasters was seen in patients and family members relative to healthy controls. Among patients, non-tasters exhibited increased levels of negative and first-rank symptoms as well as poorer right nostril odor identification skills relative to PTC tasters. These differences were not explained by age, sex, education, smoking, or intensity differences. Phenotypic variation in PTC sensitivity is thought to be genetic in origin and suggests greater illness risk for those subjects with recessive taster alleles.
-
Phenylthiocarbamide perception in patients with schizophrenia and first degree family members
American Journal of Psychiatry, 2005Co-Authors: Paul J. Moberg, Stephen J. Kanes, Raquel E. Gur, Catherine C Balderston, David R Roalf, Bruce I. TuretskyAbstract:OBJECTIVE: The inability to taste Phenylthiocarbamide (PTC) has been associated with medical and neurological illnesses not typically related to taste. The authors examined PTC sensitivity in schizophrenia patients and their non-ill relatives to determine whether this represented a vulnerability marker. METHOD: PTC sensitivity was assessed in 42 schizophrenia patients, 23 healthy comparison subjects, and 12 first-degree relatives of the patients. RESULTS: More nontasters were found among patients and family members than healthy comparison subjects. Among patients, nontasters had more positive symptoms. Differences were not explained by sex, age, medication, smoking, or cognitive impairment. CONCLUSIONS: The prevalence of PTC nontasters was greater among schizophrenia patients and non-ill first-degree family members. Phenotypic variation in PTC sensitivity is genetic in origin. This suggests a higher risk for illness among subjects with recessive alleles.
Wolfgang Meyerhof - One of the best experts on this subject based on the ideXlab platform.
-
RESEARCH ARTICLE Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception
2016Co-Authors: Natacha Roudnitzky, Maik Behrens, Anika Engel, Susann Kohl, Sophie Thalmann, Ra Hübner, Kristina Lossow, Stephen P. Wooding, Wolfgang MeyerhofAbstract:The ability to taste bitterness evolved to safeguard most animals, including humans, against potentially toxic substances, thereby leading to food rejection. Nonetheless, bitter perception is subject to individual variations due to the presence of genetic functional polymorphisms in bitter taste receptor (TAS2R) genes, such as the long-known association between genetic polymorphisms in TAS2R38 and bitter taste perception of Phenylthiocarbamide. Yet, due to overlaps in specificities across receptors, such associations with a single TAS2R locus are uncommon. Therefore, to investigate more complex associations, we examined taste responses to six structurally diverse compounds (absinthin, amarogentin, cascarillin, groshei-min, quassin, and quinine) in a sample of the Caucasian population. By sequencing all bitter receptor loci, inferring long-range haplotypes, mapping their effects on phenotype variation, and characterizing functionally causal allelic variants, we deciphered at the molecular level how a subjects ’ genotype for the whole-family of TAS2R genes shapes variation in bitter taste perception. Within each haplotype block implicated in phenotypic variation, we provided evidence for at least one locus harboring functional polymorphic alleles, e.g. one locus fo
-
coarse grained molecular mechanics of the tas2r38 bitter taste receptor experimentally validated detailed structural prediction of agonist binding
PLOS ONE, 2013Co-Authors: Alessandro Marchiori, Maik Behrens, Luciana Capece, Alejandro Giorgetti, Paolo Gasparini, Paolo Carloni, Wolfgang MeyerhofAbstract:Bitter molecules in humans are detected by ∼25 G protein-coupled receptors (GPCRs). The lack of atomic resolution structure for any of them is complicating an in depth understanding of the molecular mechanisms underlying bitter taste perception. Here, we investigate the molecular determinants of the interaction of the TAS2R38 bitter taste receptor with its agonists Phenylthiocarbamide (PTC) and propylthiouracil (PROP). We use the recently developed hybrid Molecular Mechanics/Coarse Grained (MM/CG) method tailored specifically for GPCRs. The method, through an extensive exploration of the conformational space in the binding pocket, allows the identification of several residues important for agonist binding that would have been very difficult to capture from the standard bioinformatics/docking approach. Our calculations suggest that both agonists bind to Asn103, Phe197, Phe264 and Trp201, whilst they do not interact with the so-called extra cellular loop 2, involved in cis-retinal binding in the GPCR rhodopsin. These predictions are consistent with data sets based on more than 20 site-directed mutagenesis and functional calcium imaging experiments of TAS2R38. The method could be readily used for other GPCRs for which experimental information is currently lacking.
-
the molecular basis of individual differences in Phenylthiocarbamide and propylthiouracil bitterness perception
Current Biology, 2005Co-Authors: Bernd Bufe, Dennis Drayna, Danielle R Reed, Paul A S Breslin, Christian Kuhn, Christopher D Tharp, Jay Patrick Slack, Wolfgang MeyerhofAbstract:Abstract Individual differences in perception are ubiquitous within the chemical senses: taste, smell, and chemical somesthesis [1–4]. A hypothesis of this fact states that polymorphisms in human sensory receptor genes could alter perception by coding for functionally distinct receptor types [1, 5–8]. We have previously reported evidence that sequence variants in a presumptive bitter receptor gene (h TAS2R38 ) correlate with differences in bitterness recognition of Phenylthiocarbamide (PTC) [9–11]. Here, we map individual psychogenomic pathways for bitter taste by testing people with a variety of psychophysical tasks and linking their individual perceptions of the compounds PTC and propylthiouracil (PROP) to the in vitro responses of their TAS2R38 receptor variants. Functional expression studies demonstrate that five different haplotypes from the h TAS2R38 gene code for operatively distinct receptors. The responses of the three haplotypes we also tested in vivo correlate strongly with individuals' psychophysical bitter sensitivities to a family of compounds. These data provide a direct molecular link between heritable variability in bitter taste perception to functional variations of a single G protein coupled receptor that responds to compounds such as PTC and PROP that contain the N-C=S moiety. The molecular mechanisms of perceived bitterness variability have therapeutic implications, such as helping patients to consume beneficial bitter-tasting compounds—for example, pharmaceuticals and selected phytochemicals.
Shana Adise - One of the best experts on this subject based on the ideXlab platform.
-
variation in the ability to taste bitter thiourea compounds implications for food acceptance dietary intake and obesity risk in children
Annual Review of Nutrition, 2016Co-Authors: Kathleen L Keller, Shana AdiseAbstract:The ability to taste bitter thiourea compounds, such as Phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), is inherited. Polymorphisms in the bitter-taste receptor TAS2R38 explain the majority of phenotypic variation in the PROP phenotype. It has been hypothesized that the PROP phenotype is a marker for perception of a variety of chemosensory experiences. In this review, we discuss studies that have investigated the relationship between bitter-taste response and dietary behaviors and chronic health in children. Investigators have hypothesized that children who are PROP tasters have lower liking and consumption of bitter foods, such as cruciferous vegetables. Additionally, several studies suggest that children who are unable to taste PROP (i.e., nontasters) like and consume more dietary fat and are prone to obesity. The relationship between the PROP phenotype and obesity is influenced by multiple confounders, including sex, food access, ethnicity, and socioeconomic status. Future studies that adjus...
-
variation in the ability to taste bitter thiourea compounds implications for food acceptance dietary intake and obesity risk in children
Annual Review of Nutrition, 2016Co-Authors: Kathleen L Keller, Shana AdiseAbstract:The ability to taste bitter thiourea compounds, such as Phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), is inherited. Polymorphisms in the bitter-taste receptor TAS2R38 explain the majority of phenotypic variation in the PROP phenotype. It has been hypothesized that the PROP phenotype is a marker for perception of a variety of chemosensory experiences. In this review, we discuss studies that have investigated the relationship between bitter-taste response and dietary behaviors and chronic health in children. Investigators have hypothesized that children who are PROP tasters have lower liking and consumption of bitter foods, such as cruciferous vegetables. Additionally, several studies suggest that children who are unable to taste PROP (i.e., nontasters) like and consume more dietary fat and are prone to obesity. The relationship between the PROP phenotype and obesity is influenced by multiple confounders, including sex, food access, ethnicity, and socioeconomic status. Future studies that adjust for these variables are needed.
Paul J. Moberg - One of the best experts on this subject based on the ideXlab platform.
-
Phenylthiocarbamide ptc perception in ultra high risk for psychosis participants who develop schizophrenia testing the evidence for an endophenotypic marker
Psychiatry Research-neuroimaging, 2012Co-Authors: Warrick J Brewer, Paul J. Moberg, Ashleigh Lin, Gregory Smutzer, Barnaby Nelson, Alison R Yung, Christos Pantelis, Patrick D Mcgorry, Bruce I. TuretskyAbstract:Reports suggesting that schizophrenia participants are more likely to be Phenylthiocarbamide (PTC) non-tasters when compared to controls have recently been controversial. If supported, a genetic-based phenotypic variation in PTC taster status is implicated, suggesting a greater illness risk for those participants with recessive alleles for the TAS2R38 receptor. Should PTC insensitivity be a schizophrenia endophenotype, then it would be expected in follow-up of ultra high-risk for psychosis participants who later develop schizophrenia (UHR-S). UHR-S was hypothesised to show reduced PTC sensitivity compared to those who were previously at risk, but did not transition (UHR-NP). PTC perception was assessed in 219 UHR participants at long-term follow-up, of whom 53 had transitioned to psychosis (UHR-P) during the follow-up period. Fifteen of the 219 participants were diagnosed with schizophrenia. Seventy-eight had a family history of psychotic disorder. No differences in PTC taster status were found in UHR participants based upon transition to psychosis status, schizophrenia diagnosis, or family history of schizophrenia. This report indicates that schizophrenia development among UHR participants is not associated with PTC tasting deficits and fails to support previous findings that inability to detect the bitter taste of PTC is a schizophrenia endophenotype.
-
Association of schizophrenia with the Phenylthiocarbamide taste receptor haplotype on chromosome 7q.
Psychiatric genetics, 2012Co-Authors: Paul J. Moberg, Stephen J. Kanes, Raquel E. Gur, Vidyulata Kamath, Bruce I. TuretskyAbstract:Phenylthiocarbamide (PTC) taste sensitivity is an inherited trait determined primarily by allelic variation of the taste-receptor gene TAS2R38 on chromosome 7q. Results of prior studies examining the ability to taste PTC in patients with schizophrenia have been mixed because of the difficulties in measuring PTC taste sensitivity behaviorally. In the current study, we examined the TAS2R38 genotypes of schizophrenia patients to determine whether the increased prevalence of nontasters in this patient population was indicative of a specific genetic association. Our a-priori hypothesis was that schizophrenia patients would show an increased prevalence of the nontaster phenotype compared with controls. The genotypes of two nonsynonymous coding single-nucleotide polymorphisms in TAS2R38 were assayed for 176 schizophrenia patients and 229 healthy control individuals, and the two-allele haplotypes were estimated. There was an over-representation of the major PTC nontaster haplotype among patients of European descent, relative to control individuals of similar ancestry. Patients and controls of African ancestry did not differ. The PTC nontaster haplotype is a genetic marker that may be used to identify subsets of schizophrenia patients who potentially harbor vulnerability genes in this region of chromosome 7q.
-
Phenylthiocarbamide ptc perception in parkinson disease
Cognitive and Behavioral Neurology, 2007Co-Authors: Paul J. Moberg, Catherine C Balderston, Jacqueline Rick, David R Roalf, Daniel Weintraub, Galit Kleinerfisman, Matthew B Stern, John E DudaAbstract:Objective: To examine Phenylthiocarbamide (PTC) sensitivity in Parkinson disease (PD) patients and healthy volunteers to determine whether taster status represented a simple vulnerability marker for PD. Background: The inability to taste PTC has been associated with a number of medical illnesses not typically associated with taste impairment. Abnormalities in the function/expression of G protein-signaling pathways have been implicated in PTC perception and also in dopamine expression and regulation in PD. No study has yet probed whether PTC tasting is disrupted in PD. Method: PTC sensitivity was assessed in a small sample of 36 male PD patients and 20 healthy male comparison subjects using a standardized psychophysical method. Results: A higher proportion of nontasters were found in patients relative to healthy comparison subjects. These differences were not explained by alterations in perception of basic taste intensity or age. Among patients, nontasters and tasters of PTC did not differ with regard to duration of illness, age of onset, severity of motor symptoms, or overall illness severity. Conclusions: These data suggest an increase in the frequency of PTC nontaster status in PD. As phenotypic variation in PTC sensitivity is genetic in origin, this may represent a surrogate risk factor for the development of PD.
-
Phenylthiocarbamide ptc perception in patients with schizophrenia and first degree family members relationship to clinical symptomatology and psychophysical olfactory performance
Schizophrenia Research, 2007Co-Authors: Paul J. Moberg, Stephen J. Kanes, Catherine C Balderston, David R Roalf, Colleen Mcgue, Christian G Kohler, Bruce I. TuretskyAbstract:The inability to taste Phenylthiocarbamide (PTC; “taste-blindness”) has been associated with a number of medical and neurological illnesses not typically related to taste. We examined PTC sensitivity in 67 schizophrenia patients, 30 healthy controls, and 30 first-degree relatives to determine whether taster status could represent a simple vulnerability marker. A higher prevalence of non-tasters was seen in patients and family members relative to healthy controls. Among patients, non-tasters exhibited increased levels of negative and first-rank symptoms as well as poorer right nostril odor identification skills relative to PTC tasters. These differences were not explained by age, sex, education, smoking, or intensity differences. Phenotypic variation in PTC sensitivity is thought to be genetic in origin and suggests greater illness risk for those subjects with recessive taster alleles.
-
Phenylthiocarbamide perception in patients with schizophrenia and first degree family members
American Journal of Psychiatry, 2005Co-Authors: Paul J. Moberg, Stephen J. Kanes, Raquel E. Gur, Catherine C Balderston, David R Roalf, Bruce I. TuretskyAbstract:OBJECTIVE: The inability to taste Phenylthiocarbamide (PTC) has been associated with medical and neurological illnesses not typically related to taste. The authors examined PTC sensitivity in schizophrenia patients and their non-ill relatives to determine whether this represented a vulnerability marker. METHOD: PTC sensitivity was assessed in 42 schizophrenia patients, 23 healthy comparison subjects, and 12 first-degree relatives of the patients. RESULTS: More nontasters were found among patients and family members than healthy comparison subjects. Among patients, nontasters had more positive symptoms. Differences were not explained by sex, age, medication, smoking, or cognitive impairment. CONCLUSIONS: The prevalence of PTC nontasters was greater among schizophrenia patients and non-ill first-degree family members. Phenotypic variation in PTC sensitivity is genetic in origin. This suggests a higher risk for illness among subjects with recessive alleles.
Dennis Drayna - One of the best experts on this subject based on the ideXlab platform.
-
A potential trigger for pine mouth: A case of a homozygous Phenylthiocarbamide taster
Nutrition Research, 2015Co-Authors: Davide S. Risso, Carter Vanwaes, Louisa Howard, Dennis DraynaAbstract:Pine mouth, also known as pine nut syndrome, is an uncommon dysgeusia that generally begins 12 to 48 hours after consuming pine nuts. It is characterized by a bitter metallic taste, usually amplified by the consumption of other foods, which lasts 2 to 4 weeks. Recent findings have correlated this disorder with the consumption of nuts of the species Pinus armandii, but no potential triggers or common underlying medical causes have been identified in individuals affected by this syndrome. We report a 23-year-old patient affected by pine mouth who also underwent a Phenylthiocarbamide taste test and was found to be a taster for this compound. TAS2R38 genotyping demonstrated that this subject was a homozygous carrier of the proline-alanine-valine taster haplotype.We, therefore, hypothesize that homozygous Phenylthiocarbamide taster status may be a potential contributor for pine mouth events. Although based on a single observation, this research suggests a connection between genetically determined bitter taste perception and the occurrence of pine nut dysgeusia events.
-
associations between Phenylthiocarbamide gene polymorphisms and cigarette smoking
Nicotine & Tobacco Research, 2005Co-Authors: Dale S Cannon, Dennis Drayna, Timothy B Baker, Megan E Piper, Mary Beth Scholand, Daniel L Lawrence, William M Mcmahon, Martin G Villegas, Trace C Caton, Hilary CoonAbstract:Phenotypic evidence indicates that the ability to taste the bitter compounds Phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) may protect against cigarette smoking. In this study, PTC gene haplotypes were found to be associated with both the odds of being a smoker and the importance of cigarette taste as a smoking motive. Smokers (n = 384) and nonsmokers (n = 183) were genotyped for polymorphisms that affect taste sensitivity to PTC and PROP. The "taster" PAV haplotype, relative to the "nontaster" AVI haplotype, was predicted to be associated with reduced odds of being a smoker and lower taste motivation as measured by the Wisconsin Inventory of Smoking Dependence Motives-68 taste/sensory processes scale. The results did not support the predicted association between the PAV and AVI haplotypes and smoker odds, but the AAV haplotype, which confers intermediate PTC/PROP taste sensitivity, was associated with reduced smoker prevalence (49% vs. 70%), chi(2)(1, N = 567) = 10.392, p = .001. The predicted relationship between PAV and AVI and taste motivation was found, F(2, 348) = 3.303, p = .038. The results encourage further exploration of the role of taste/sensory processes in tobacco dependence.
-
the molecular basis of individual differences in Phenylthiocarbamide and propylthiouracil bitterness perception
Current Biology, 2005Co-Authors: Bernd Bufe, Dennis Drayna, Danielle R Reed, Paul A S Breslin, Christian Kuhn, Christopher D Tharp, Jay Patrick Slack, Wolfgang MeyerhofAbstract:Abstract Individual differences in perception are ubiquitous within the chemical senses: taste, smell, and chemical somesthesis [1–4]. A hypothesis of this fact states that polymorphisms in human sensory receptor genes could alter perception by coding for functionally distinct receptor types [1, 5–8]. We have previously reported evidence that sequence variants in a presumptive bitter receptor gene (h TAS2R38 ) correlate with differences in bitterness recognition of Phenylthiocarbamide (PTC) [9–11]. Here, we map individual psychogenomic pathways for bitter taste by testing people with a variety of psychophysical tasks and linking their individual perceptions of the compounds PTC and propylthiouracil (PROP) to the in vitro responses of their TAS2R38 receptor variants. Functional expression studies demonstrate that five different haplotypes from the h TAS2R38 gene code for operatively distinct receptors. The responses of the three haplotypes we also tested in vivo correlate strongly with individuals' psychophysical bitter sensitivities to a family of compounds. These data provide a direct molecular link between heritable variability in bitter taste perception to functional variations of a single G protein coupled receptor that responds to compounds such as PTC and PROP that contain the N-C=S moiety. The molecular mechanisms of perceived bitterness variability have therapeutic implications, such as helping patients to consume beneficial bitter-tasting compounds—for example, pharmaceuticals and selected phytochemicals.
-
bitter taste study in a sardinian genetic isolate supports the association of Phenylthiocarbamide sensitivity to the tas2r38 bitter receptor gene
Chemical Senses, 2004Co-Authors: Dionigio Prodi, Dennis Drayna, Paola Forabosco, Maria Antonietta Palmas, Giovanni Battista Maestrale, Daniela Piras, M Pirastu, Andrea AngiusAbstract:Recently, a major locus on chromosome 7q was found in association with the taste sensitivity to Phenylthiocarbamide (PTC) in humans. This region contains the TAS2R38 gene that encodes a member of the TAS2R bitter taste receptor family. Three SNPs within this gene demonstrated a strong association with taster status in Utah families and in an additional sample of 85 unrelated individuals. We studied a small isolated village in eastern Sardinia and carried out a genome-wide scan to map the genetic basis of PTC perception in this population. We performed both qualitative and quantitative PTC-taste linkage analysis. Qualitative analysis was carried out by defining a cut-off from the bimodal distribution of the trait and classifying subjects as tasters and non-tasters (75 and 25%, respectively). Linkage analysis on 131 subjects belonging to a unique large multi-generation pedigree comprising 239 subjects confirmed significant evidence for linkage at 7q35 also in our population. Haplotype analyses of the three SNPs inside the PTC gene allowed us to identify only two haplotypes that were associated with the non-taster phenotype (80% AVI homozygous) and to taster phenotype (40% PAV homozygous and 56% PAV/AVI heterozygous). Sex, age and haplotype effect explained 77.2 % of the total variance in PTC sensitivity.
-
positional cloning of the human quantitative trait locus underlying taste sensitivity to Phenylthiocarbamide
Science, 2003Co-Authors: Eric Jorgenson, Hilary Coon, M Leppert, Neil Risch, Dennis DraynaAbstract: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.