Awards from the National Institutes of Health supported this research (R01DC013588 to NAC, R21DC013886 to NAC and DRR, and NIDCD Administrative Research Supplement to Promote Emergence of Clinician-Scientists in Chemosensory Research to JED). We collected genotype data from equipment purchased in part with NIH funds from OD018125.

The University of Pennsylvania Institutional Review board approved this protocol. We excluded subjects if they were under 18 years of age or were pregnant.
1. Oral Cavity Evaluation: Disease Assessment and Papilla Identification
<ol>
	<li>Instruct the subject to open the mouth.</li>
	<li>Using a light source such as a penlight or headlamp, illuminate the oral cavity and examine the seven subsites of the area (tongue, floor of mouth, buccal mucosa, labial mucosa, gingiva, hard palate,...

<ol>
	<li>Cowart, B. J., Young, I. M., Feldman, R. S., Lowry, L. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+disorders+of+smell+and+taste.">Clinical disorders of smell and taste.</a> Occupational Medicine. 12 (3), 465-483 (1997).</li><li>Ackerman, B. H., Kasbekar, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Disturbances+of+taste+and+smell+induced+by+drugs.">Disturbances of taste and smell induced by drugs.</a> Pharmacotherapy. 17 (3), 482-496 (1997).</li><li>Kveton, J. F., Bartoshuk, L. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+effect+of+unilateral+chorda+tympani+damage+on+taste.">The effect of unilateral chorda tympani damage on taste.</a> Laryngoscope. 104, 25-29 (1994).</li><li>Fischer, R. A., Griffin, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmacogenetic+aspects+of+gustation.">Pharmacogenetic aspects of gustation.</a> Drug Research. 14 (14), 673-686 (1964).</li><li>Joyce, C. R., Pan, L., Varonos, D. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Taste+sensitivity+may+be+used+to+predict+pharmacological+effects.">Taste sensitivity may be used to predict pharmacological effects.</a> Life Science. 7 (9), 533-537 (1968).</li><li>Adappa, N. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetics+of+the+taste+receptor+T2R38+correlates+with+chronic+rhinosinusitis+necessitating+surgical+intervention.">Genetics of the taste receptor T2R38 correlates with chronic rhinosinusitis necessitating surgical intervention.</a> International Forum of Allergy &amp; Rhinology. , (2013).</li><li>Lipchock, S. V., Reed, D. R., Mennella, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relationship+between+bitter-taste+receptor+genotype+and+solid+medication+formulation+usage+among+young+children:+a+retrospective+analysis.">Relationship between bitter-taste receptor genotype and solid medication formulation usage among young children: a retrospective analysis.</a> Clinical Therapeutics. 34 (3), 728-733 (2012).</li><li>Bartoshuk, L. M., Carterette, E. C., Friedman, M. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Handbook of perception: Tasting and smelling. , 2-18 (1978).</li><li>Coldwell, S. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gustation+assessment+using+the+NIH+Toolbox.">Gustation assessment using the NIH Toolbox.</a> Neurology. 80 (11 Suppl 3), S20-S24 (2013).</li><li>Mueller, C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Quantitative+assessment+of+gustatory+function+in+a+clinical+context+using+impregnated+&amp;#34;taste+strips&amp;#34.">Quantitative assessment of gustatory function in a clinical context using impregnated &amp;#34;taste strips&amp;#34.</a> Rhinology. 41 (1), 2-6 (2003).</li><li>Reed, D. R., Tanaka, T., McDaniel, A. 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A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Denver+papillae+protocol+for+objective+analysis+of+fungiform+papillae.">Denver papillae protocol for objective analysis of fungiform papillae.</a> Journal of Visualized Experiments. (100), e52860 (2015).</li><li>Sanyal, S., O'Brien, S. M., Hayes, J. E., Feeney, E. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=TongueSim:+development+of+an+automated+method+for+rapid+assessment+of+fungiform+papillae+density+for+taste+research.">TongueSim: development of an automated method for rapid assessment of fungiform papillae density for taste research.</a> Chemical Senses. 41 (4), 357-365 (2016).</li><li>Spielman, A. I., Brand, J. G., Buischi, Y., Bretz, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Resemblance+of+tongue+anatomy+in+twins.">Resemblance of tongue anatomy in twins.</a> Twin Research and Human Genetics. 14 (3), 277-282 (2011).</li><li>Kalmus, H., Smith, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+antimode+and+lines+of+optimal+separation+in+a+genetically+determined+bimodal+distribution,+with+particular+reference+to+phenylthiocarbamide+sensitivity.">The antimode and lines of optimal separation in a genetically determined bimodal distribution, with particular reference to phenylthiocarbamide sensitivity.</a> Annals of Human Genetics. 29 (2), 127-138 (1965).</li><li>Pearson, J., Finegold, M. J., Budzilovich, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+tongue+and+taste+in+familial+dysautonomia.">The tongue and taste in familial dysautonomia.</a> Pediatrics. 45 (5), 739-745 (1970).</li><li>Fukutake, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Late-onset+hereditary+ataxia+with+global+thermoanalgesia+and+absence+of+fungiform+papillae+on+the+tongue+in+a+Japanese+family.">Late-onset hereditary ataxia with global thermoanalgesia and absence of fungiform papillae on the tongue in a Japanese family.</a> Brain. 119 (Pt 3), 1011-1021 (1996).</li><li>Kinnamon, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Taste+receptor+signalling+-+from+tongues+to+lungs.">Taste receptor signalling - from tongues to lungs.</a> Acta physiologica. 204 (2), 158-168 (2012).</li><li>Lewandowski, B. C., Sukumaran, S. K., Margolskee, R. F., Bachmanov, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amiloride-insensitive+salt+taste+is+mediated+by+two+populations+of+type+iii+taste+cells+with+distinct+transduction+mechanisms.">Amiloride-insensitive salt taste is mediated by two populations of type iii taste cells with distinct transduction mechanisms.</a> Journal of Neuroscience. 36 (6), 1942-1953 (2016).</li><li>Vandenbeuch, A., Clapp, T. R., Kinnamon, S. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Amiloride-sensitive+channels+in+type+I+fungiform+taste+cells+in+mouse.">Amiloride-sensitive channels in type I fungiform taste cells in mouse.</a> BMC Neuroscience. 9, 1 (2008).</li><li>Margolskee, R. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+biochemistry+and+molecular+biology+of+taste+transduction.">The biochemistry and molecular biology of taste transduction.</a> Current Opinions in Neurobiology. 3 (4), 526-531 (1993).</li><li>Meyerhof, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+molecular+receptive+ranges+of+human+TAS2R+bitter+taste+receptors.">The molecular receptive ranges of human TAS2R bitter taste receptors.</a> Chemical Senses. 35 (2), 157-170 (2010).</li><li>Yee, K. K., Sukumaran, S. K., Kotha, R., Gilbertson, T. A., Margolskee, R. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glucose+transporters+and+ATP-gated+K++(KATP)+metabolic+sensors+are+present+in+type+1+taste+receptor+3+(T1r3)-expressing+taste+cells.">Glucose transporters and ATP-gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells.</a> Proceedings of the National Academy of Sciences USA. , (2011).</li><li>Tordoff, M. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Calcium:+taste,+intake+and+appetite.">Calcium: taste, intake and appetite.</a> Physiological Review. 81, 1567-1597 (2001).</li><li>Reed, D. R., Xia, M. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+advances+in+fatty+acid+perception+and+genetics.">Recent advances in fatty acid perception and genetics.</a> Advances in Nutrition. 6 (3), 353S-360S (2015).</li><li>Blekhman, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Host+genetic+variation+impacts+microbiome+composition+across+human+body+sites.">Host genetic variation impacts microbiome composition across human body sites.</a> Genome Biology. 16, 191 (2015).</li><li>Hoon, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Putative+mammalian+taste+receptors:+a+class+of+taste-specific+GPCRs+with+distinct+topographic+selectivity.">Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity.</a> Cell. 96 (4), 541-551 (1999).</li><li>Laffitte, A., Neiers, F., Briand, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Functional+roles+of+the+sweet+taste+receptor+in+oral+and+extraoral+tissues.">Functional roles of the sweet taste receptor in oral and extraoral tissues.</a> Current Opinion in Clinical Nutrition and Metabolic. 17 (4), 379-385 (2014).</li><li>An, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Tas2r+activation+promotes+airway+smooth+muscle+relaxation+despite+beta2-adrenergic+receptor+tachyphylaxis.">Tas2r activation promotes airway smooth muscle relaxation despite beta2-adrenergic receptor tachyphylaxis.</a> American Journal of Physiology-Lung Cellular and Molecular. , (2012).</li><li>Fox, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+relationship+between+chemical+composition+and+taste.">The relationship between chemical composition and taste.</a> Science. 74, 607 (1931).</li><li>Fox, A. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+relationship+between+chemical+constitution+and+taste.">The relationship between chemical constitution and taste.</a> Proceedings of the National Academy of Sciences USA. 18, 115-120 (1932).</li><li>Bufe, B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+molecular+basis+of+individual+differences+in+phenylthiocarbamide+and+propylthiouracil+bitterness+perception.">The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception.</a> Current Biol.ogy. 15 (4), 322-327 (2005).</li><li>Reed, D. R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+perception+of+quinine+taste+intensity+is+associated+with+common+genetic+variants+in+a+bitter+receptor+cluster+on+chromosome+12.">The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12.</a> Human Molecular Genetics. 19 (21), 4278-4285 (2010).</li><li>Bobowski, N., Reed, D. R., Mennella, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Variation+in+the+TAS2R31+bitter+taste+receptor+gene+relates+to+liking+for+the+nonnutritive+sweetener+Acesulfame-K+among+children+and+adults.">Variation in the TAS2R31 bitter taste receptor gene relates to liking for the nonnutritive sweetener Acesulfame-K among children and adults.</a> Science Reports. 6, 39135 (2016).</li><li>Allen, A. L., McGeary, J. E., Knopik, V. S., Hayes, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bitterness+of+the+non-nutritive+sweetener+acesulfame+potassium+varies+with+polymorphisms+in+TAS2R9+and+TAS2R31.">Bitterness of the non-nutritive sweetener acesulfame potassium varies with polymorphisms in TAS2R9 and TAS2R31.</a> Chemical Senses. 38 (5), 379-389 (2013).</li><li>Roudnitzky, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genomic,+genetic,+and+functional+dissection+of+bitter+taste+responses+to+artificial+sweeteners.">Genomic, genetic, and functional dissection of bitter taste responses to artificial sweeteners.</a> Human Molecular Genetics. 20 (17), 3437-3449 (2011).</li><li>Guo, S. W., Reed, D. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+genetics+of+phenylthiocarbamide+perception.">The genetics of phenylthiocarbamide perception.</a> Annals in Human Biology. 28 (2), 111-142 (2001).</li><li>Bartoshuk, L. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Labeled+scales+(e.g.,+category,+Likert,+VAS)+and+invalid+across-group+comparisons:+what+we+have+learned+from+genetic+variation+in+taste.">Labeled scales (e.g., category, Likert, VAS) and invalid across-group comparisons: what we have learned from genetic variation in taste.</a> Food Quality Prefererences. 14 (2), 125-138 (2003).</li></ol>

NAC and DRR are co-inventors on a patent under review (Therapy and Diagnostics for Respiratory Infection 61/697,652, WO2013112865).

The significance of this method is that it uses a multidisciplinary approach with features from medicine (the oral exam), experimental psychology (the taste test) and genetics (a validation step). Taste information is likely to develop as a diagnostic and prognostic tool because taste provides a window into the function of proteins elsewhere in the body. From an experimental psychology viewpoint, the addition of a simple exam can identify subjects who are not appropriate for the study of normative taste function. From a ...

Measures of human taste perception can be both part of medical care and a target of biomedical research, yet taste has received scant attention compared with hearing and vision (Table 1). From the medical perspective, when clinicians evaluate patients complaining of taste loss, in most cases the actual loss is of smell1, which has led to dismissal of taste loss as an uncommon and often invalid presenting complaint. Taste distortions (dysgeusia) are more common and frequently arise from the secondary effects of medications or peripheral nerve injury2,3, but neither form has an effective treatment (other than stopping the medication). Clinicians have also ignored taste loss because it has hitherto had little diagnostic or prognostic value on its own. However, although the measurement of taste has been a backwater, it may now be entering mainstream medicine with the revival of a historical appreciation that taste may be a diagnostic or prognostic tool4,5. For instance, bitterness perception can predict immune function6 or the willingness of a patient to take medication7. Nonetheless, biomedical researchers have largely neglected taste. This inattention may, in part, reflect the fact that early progress in understanding this sensory system has its roots in experimental psychology8, a field with which those in medicine may be relatively unfamiliar. Moreover, renewed interest in taste has ushered in standardized taste methods9 that build on earlier methods10, which while comprehensive are lengthy and inappropriate for clinical settings. Finally, confidence in taste measures can be weak because subjects report on their own experience and validation of their observations has hitherto been lacking. Our hope is that a simple measure that investigators or clinicians can easily administer will gain in popularity with both constituents. Here we describe a simple taste exam protocol that has three parts: an assessment of the oral cavity, the taste test, and a validation step using inborn genotype. First, we provide biological context for these procedures, which merge simple practices in medicine, sensory measures from experimental psychology and validation of responses using genotype and genetics.
Taste perception starts in the mouth, so an effective taste exam needs to include a brief clinical assessment for obvious oral diseases, redness, swelling and other discoloration. The oral cavity contains seven subsites: the tongue, gingiva, floor of mouth, buccal mucosa, labial mucosa, hard palate, and the retromolar trigone. Past studies of human taste focused on healthy participants or those with well-defined diseases, but as taste testing becomes routine in medical exams, it is important to record the condition of the oral cavity as part of the procedure.
The tongue itself is a muscular structure encased in mucosa; dotting its dorsal surface are papillae, the small raised structures that give the tongue its unique texture and contain taste receptor cells. We classify papillae by their shape: fungiform, filiform, foliate, and circumvallate. Fungiform papillae (FP) are located anterolaterally on the tongue and are round, with a mushroom shape11. Investigators have published several useful methods to quantify FP and we direct readers to these sources for measurement protocols12,13,14,15,16. Foliate papillae, shaped like the pages of a book (folia), are located exclusively on the lateral posterior tongue surface11. Circumvallate papillae, found in the sulcus terminalis of the tongue base, are large dome-shaped structures surrounded by mucosal walls (Latin circum, &#34;surround,&#34; + vallum, &#34;wall&#34;)11. The most numerous papillae, the filiform, are long and thin and do not contain taste receptors.
People differ in tongue anatomy. While the sources of this anatomic variation are unknown, it is determined in part by inborn genetic variation, with investigators reporting 31% concordance of tongue anatomy among dizygotic twins and 60% concordance among monozygotic twins17. Papillary density also differs among people, and although rare, at least one genetic disease (familial dysautonomia) results in a congenital absence of taste papillae18,19,20. Thus, before performing psychophysical testing, it is helpful to confirm the presence of FP as part of the brief assessment and note the relative size and color of the tongue and evidence of oral disease.
The taste papillae contain the sensory cells that when stimulated initiate taste sensation. Humans are capable of sensing at least five classes of taste: salty, sour, bitter, sweet, and umami. While salty, sweet, and umami tastes signal the presence of valuable food sources containing sodium chloride, glucose, and amino acids, respectively, bitterness and sourness signal the presence of potential toxins and acids from the bacterial decomposition of food, respectively, and induce aversive behavior21. Salty and sour tastes are transduced through the activation of ion channels found in some types of taste cells, though the understanding of salt transduction is evolving and it may require type I cells as well22,23. Bitter, sweet, and umami arise from activation of G-protein-coupled receptors on type II taste cells, each attuned to a particular taste. Heterodimers of subunits of three particular receptors transduce sweet and umami while bitter compounds activate a group of 25 different bitter receptors24. These bitter receptors can respond to multiple bitter compounds, and a single bitter compound often stimulates more than one receptor25. Despite the recent expansion of knowledge about the molecular basis of taste, novel pathways26 and new discoveries beyond the traditional five taste qualities (e.g., calcium27 or fatty acid28 perception) may lie ahead.
There are at least two surprising aspects of the taste families of receptors: genes that code for these receptors can differ markedly in DNA sequence and hence function among people, and many tissues of the body express these genes21,29,30,31. These extraoral sites include the brain, thyroid, upper and lower respiratory tract, and the gastrointestinal tract, among many others21,29,30,31. While the taste receptors at these locations do not participate in taste perception in the traditional sense, they likely sense the local chemical environment29,32. For example, the ciliated epithelium of the upper respiratory tract expresses the bitter receptor T2R38 (Bitter Taste Receptor 38), which responds to chemical compounds produced by bacteria and influences the innate immune response32, such as increasing mucociliary clearance and levels of anti-microbial peptides and nitric oxide. This finding has medical implications for chronic rhinosinusitis, a disease of chronic bacterial infection and inflammation of the upper respiratory tract and paranasal sinuses.
Of particular relevance to the taste exam we describe here is that the T2R38 bitter taste receptor, encoded by the TAS2R38 gene, exhibits genetic variability and therefore variable taste sensitivity. Perceptual differences for the bitter compound phenylthiocarbamide (PTC) were first described by the chemist Arthur Fox33; later this compound was identified as an agonist of the T2R38 receptor34. Individual differences arise from the DNA sequence of the TAS2R38 gene, which has three single-nucleotide polymorphisms, each yielding amino acid substitutions (A49P, A262V, and I296V; A: Alanine, P: Proline, V: Valine, I: Isoleucine). Two common haplotypes result, PAV and AVI, with PAV/PAV individuals being highly sensitive to PTC (&#34;tasters&#34;), AVI/AVI individuals being relatively insensitive (&#34;non-tasters&#34;), and heterozygous AVI/PAV individuals being more variable in their sensitivity35. There are more examples of genetic variation affecting bitter perception, e.g., taste receptor T2R19, encoded by the TAS2R19 gene, similarly exhibits genetic variability and differing taste sensitivity to the bitter compound quinine36. Likewise, variation in TAS2R31 affects the perceived bitterness of one of the high-potency sweeteners37,38,39.
Here we describe a rapid method to characterize a patient&#39;s sense of taste that draws on high-yield protocols in clinical medicine, experimental psychology and genetics.

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		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">Phenylthiocarbamide</td>
			<td>Sigma Aldrich</td>
			<td>P7629</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">Quinine hydrochloride dihydrate</td>
			<td>Sigma Aldrich</td>
			<td>Q1125</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">Sodium Chloride</td>
			<td>Sigma Aldrich</td>
			<td>S1679</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:307px;">Sucrose</td>
			<td>Sigma Aldrich</td>
			<td>S0389</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Glass scintillation vials</td>
			<td>Thomas Scientific</td>
			<td>1230L59</td>
			<td>Same as Wheaton catalog no. 986580</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Oragene Discover OGR-500 DNA collection kit</td>
			<td>DNA Genotek</td>
			<td style="width:124px;">OGR-500</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">prepIT L2P Protocol reagents</td>
			<td>DNA Genotek</td>
			<td>PT-L2P-5</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">rs713598 TaqMan SNP genotyping assay</td>
			<td>ThermoFisher Scientific</td>
			<td>C___8876467_10</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">rs1726866 TaqMan SNP genotyping assay</td>
			<td>ThermoFisher Scientific</td>
			<td>C___9506827_10</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">rs10246939 TaqMan SNP genotyping assay</td>
			<td>ThermoFisher Scientific</td>
			<td>C___9506826_10</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">rs10772420 TaqMan SNP genotyping assay</td>
			<td>ThermoFisher Scientific</td>
			<td>C___1317426_10</td>
			<td></td>
		</tr>
	</tbody>
</table>

taste exam: a brief and validated test

The emerging importance of taste in medicine and biomedical research, and new knowledge about its genetic underpinnings, has motivated us to supplement classic taste-testing methods in two ways. First, we explain how to do a brief assessment of the mouth, including the tongue, to ensure that taste papillae are present and to note evidence of relevant disease. Second, we draw on genetics to validate taste test data by comparing reports of perceived bitterness intensity and inborn receptor genotypes. Discordance between objective measures of genotype and subjective reports of taste experience can identify data collection errors, distracted subjects or those who have not understood or followed instructions. Our expectation is that fast and valid taste tests may persuade researchers and clinicians to assess taste regularly, making taste testing as common as testing for hearing and vision. Finally, because many tissues of the body express taste receptors, taste responses may provide a proxy for tissue sensitivity elsewhere in the body and, thereby, serve as a rapid, point-of-care test to guide diagnosis and a research tool to evaluate taste receptor protein function.

Results from the taste test have been pooled for all subjects evaluated (n = 840) and are presented after segregation by genotype. The full data set is accessible at https://carayata.shinyapps.io/TasteBoxplots/ and can be reviewed for each tastant assessed and for TAS2R38 and TAS2R19 genotypes. Results confirm the existence of perceptual taste differences for PTC among subjects grouped by TAS2R38 receptor genotype (Figure 3). Rating...

Watch this Scientific Journal Video about Taste Exam: A Brief and Validated Test at JoVE.com

Taste Exam: A Brief and Validated Test

This protocol measures human taste responses and includes a brief anatomical assessment, a short taste test, and a validation method using the subject&#39;s reported sensation and taste receptor genotype.

The emerging importance of taste in medicine and biomedical research, and new knowledge about its genetic underpinnings, has motivated us to supplement ...

This method can help answer key questions in the medical and sensory field about each person's sense of taste. The main advantage of this technique is its brevity and suitability for biomedical research. The implications of this technique extend towards the diagnosis and treatment of chronic rhino sinusitis because taste receptors are part of the innate immune system.I will be demonstrating the procedure on our lab member David and Lauren will be making the taste solutions. Begin by instructing the subject to open their mouth. Use a light to illuminate the oral cavity and examine the seven sub-sites of the area.Here the dorsal tongue is easily visible. Using a tongue depressor to depress the tongue the posterior pharynx becomes visible. Next lateralizing the tongue allows exposure of the left retromolar trigone and the left buccal mucosa.Here the anterior gingiva and the labial mucosa are visualized. As the subject's tongue is lifted the ventral tongue surface becomes visible. And this allows for examination of the subjects floor of mouth.The tongue is then lateralized again to examine the right retromolar trigone and the right buccal mucosa. And lastly the hard and soft palate are visualized. Note lesions, abrasions, and masses or signs of inflammation.Use a light source to visualize the dorsal surface of the tongue and identify the presence or absence of fungiform papillae or smooth surface of the tongue. Finally write down the results of oral cavity examination before proceeding with taste testing. Begin by preparing the taste solutions using a volumetric flask for each to ensure precision of concentrations.Dissolve samples using ultra pure water. Wrap any light sensitive solutions with foil to reduce exposure to light. Then store the taste solutions at four degrees Celsius.To identify common errors in solution preparation fill one tasting cup with the old solution and one with the new solution. Taste each solution to verify they are identical in strength. Next, label vial caps with a circular sticker according to the order of presentation and a color code.In order to match the vial labels with the labels on the taste questionnaire. Package samples by placing them into their respective carriers. Next prepare the taste questionnaire using a category scale for rating taste intensity and a forced choice for identifying the taste quality of each tastant.Lastly, place circular labels of the appropriate color and number next to the appropriate sample in the taste questionnaire. Provide the subject with the sample box, a bottle of water, an empty cup, pen, and taste questionnaire containing entries for 12 samples. Explain the testing procedure and inform the subject that they will be asked to rate both the intensity and quality of each tastant.Let them know that they may not experience all qualities. Start the test by asking the subject to rinse their mouth twice with water and spit it out in the cup provided. Have them pour all of sample one into their mouth and hold it there for five seconds before spitting the solution into the cup.Tell them not to gargle or swallow the solution. Then instruct the subject to circle one of the 13 vertical lines corresponding with the sample's intensity. On a scale of 0 to 12.From no intensity at all to extremely intense. And choose a single quality to describe the taste. Next ask the subject to rinse their mouth with water twice before proceeding to the next sample.Observe the subject tasting and rating sample one of water. Should the rating deviate from no intensity at all and no flavor, reiterate the questionnaire instructions before allowing the test to proceed. After all samples have been tasted review the finished questionnaire for completeness.Finally, score intensity ratings on a scale of 0 to 12 from the vertical lines that the subject circled. And average the two intensity ratings for each tastant for later analysis. Results of the taste test confirm the existence of perceptual taste differences for the bitter compound, Phenylthiocarbamide or PTC among subjects grouped by the TAS2R38 receptor genotype.Ratings of PTC intensity are significantly different across three genotypes. The motivation behind this study was to try to assess or to develop a rapid point of service exam that we could do in the clinic that would assess the function of this receptor that we believe plays a role in the development of chronic sinusitis. The idea here is could we use this taste test to predict which of our patients are at high risk for developing sinusitis and more importantly, which patients are good surgical candidates for us to do our sinus surgery on, or which ones will do poorly with our sinus surgery.So we're trying to use this taste test to prognosticate patient's sinal-nasal disease. Once that we went through all of the taste testing we confirmed that by genotyping the patients. And as you can see in figure three for the most part the patient's genotype follows the pattern of their phenotype.Meaning the more bitter they tasted they tended to be dominant for this receptor. However, there are some outliers. Showing that there are functional homozygotes, PAV/PAVs that said that they didn't taste PTC and on the flip side of that there were some nonfunctional AVI/AVI individuals that tasted PTC with bitterness.So that means that whatever taste test we do develop if there are patients that are not fulfilling our expectations that we probably wanna confirm the taste test by genotyping them for T2R38. Once mastered the exam and taste test can be performed in under 30 minutes. After watching this video you should have an understanding of how to perform an oral exam, note evidence of disease and perform a brief taste test.

Research

JoVE Journal

Medicine

16.0K visualizações.  Perelman School of Medicine at the University of Pennsylvania. This method can help answer key questions in the medical and sensory field about each person's sense of taste. The main advantage of this technique is its brevity and suitability for biomedical research. The implications of this technique extend towards the diagnosis and treatment of chronic rhino sinusitis because taste receptors are part of the innate immune system.I will be demonstrating the procedure on our lab member David and Lauren will be making the taste solutions. Begin by in...