For sensory science in general, a major goal is to understand the relationships among perceptions and the underlying sensory mechanisms at various levels; that is, to assign psychological consequences to the functions of the genes associated with the sensory system. Within bitter taste alone, there are dozens, of genes specifically involved just with detecting bitterness The daunting task of ascribing function to these genes will require a multidisciplinary approach that combines genetics and genomics with studies of perception and physiology. The ultimate long-term goal of the proposed project is to identify genes associated with specific bitter-taste sensitivities. An essential initial step towards the goals, as outlined in this proposal, is to phenotype bitter taste perception and to rigorously establish reliable individual differences. Subjects will be screened using a broad array of forced-choice and scaling techniques that examine many bitter perceptual attributes. We have now identified two robust classes of individual differences in bitterness sensitivities: (i) people who show a specific bitter insensitivity for sucrose octaacetate (SOA) and (ii) people who are totally bitter blind with otherwise normal taste. Bitter blindness is a rare trait found in three individuals thus far. SOA insensitivity appears in approximately 30% the population at large. In the present proposal, we will psychophysically screen approximately 500 subjects to identify affected SOA-insensitive probands and age, gender and race matched unaffected controls. The extended families of identified SOA-insensitive probands will be examined. Relative risk ratios, family correlations, segregation analyses and environmental and medical history interviews will be conducted to determine the heritability and, if genetic, the mode of inheritance for SOA insensitivity. The SOA study also has the advantage of examining a human phenotype that parallels the well-characterized mouse SOA insensitivity phenotype. DNA samples will be collected from all subjects, with the intention that candidate genes will be screened for polymorphisms and family-based linkage analysis conducted on a candidate region of the genome. As a second goal, 5000 subjects will be screened to determine the prevalence of bitter blindness. This novel phenotype will require extensive analysis in order to understand its impact on the perceptual taste world of affected individuals. Bitter blind probands and age, race and gender matched normal controls will be phenotyped psychophysically in' greater detail in the laboratory. The analyses of these important taste traits have the potential to reveal principles of organization of taste coding as well as underlying taste genomics.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC002995-09
Application #
6896394
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Davis, Barry
Project Start
1996-12-01
Project End
2007-06-30
Budget Start
2005-07-01
Budget End
2006-06-30
Support Year
9
Fiscal Year
2005
Total Cost
$345,489
Indirect Cost
Name
Monell Chemical Senses Center
Department
Type
DUNS #
088812565
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Hwang, Liang-Dar; Gharahkhani, Puya; Breslin, Paul A S et al. (2018) Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste. BMC Genomics 19:678
Hwang, Liang-Dar; Zhu, Gu; Breslin, Paul A S et al. (2015) A common genetic influence on human intensity ratings of sugars and high-potency sweeteners. Twin Res Hum Genet 18:361-7
Campbell, Michael C; Ranciaro, Alessia; Zinshteyn, Daniel et al. (2014) Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa. J Hum Genet 59:349-52
Campbell, Michael C; Ranciaro, Alessia; Zinshteyn, Daniel et al. (2014) Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa. Mol Biol Evol 31:288-302
Platte, Petra; Herbert, Cornelia; Pauli, Paul et al. (2013) Oral perceptions of fat and taste stimuli are modulated by affect and mood induction. PLoS One 8:e65006
Breslin, Paul A S (2013) An evolutionary perspective on food and human taste. Curr Biol 23:R409-18
Coldwell, Susan E; Mennella, Julie A; Duffy, Valerie B et al. (2013) Gustation assessment using the NIH Toolbox. Neurology 80:S20-4
Wise, Paul M; Breslin, Paul A S (2013) Individual differences in sour and salt sensitivity: detection and quality recognition thresholds for citric acid and sodium chloride. Chem Senses 38:333-42
Wise, Paul M; Breslin, Paul A S; Dalton, Pamela (2012) Sweet taste and menthol increase cough reflex thresholds. Pulm Pharmacol Ther 25:236-41
des Gachons, Catherine Peyrot; Mura, Emi; Speziale, Camille et al. (2012) Opponency of astringent and fat sensations. Curr Biol 22:R829-30

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