HUMAN BITTER TASTE: GENETICS OF PSYCHOLOGICAL TRAITS

描述(申请人提供)：一般而言，感官科学的一个主要目标是在不同层面上了解知觉之间的关系和潜在的感觉机制；即，将心理后果赋予与感觉系统相关的基因的功能。仅在苦味方面，就有数十个基因专门与检测苦味有关。将这些基因的功能归因于这些基因的艰巨任务将需要一种多学科的方法，将遗传学和基因组学与感知和生理学研究相结合。这项拟议项目的最终长期目标是确定与特定苦味敏感相关的基因。正如本提案中所概述的，朝着这些目标迈出的重要的第一步是表现出苦味的感觉，并严格建立可靠的个体差异。受试者将使用一系列强制选择和缩放技术进行筛选，这些技术检查了许多痛苦的感知属性。我们现在已经确定了两类个体在苦味敏感度上的显著差异：(I)对蔗糖八醋酸酯(SOA)表现出特殊苦味不敏感的人，以及(Ii)完全苦涩盲目、否则味道正常的人。到目前为止，在三个人身上发现了一种罕见的严重失明特征。大约30%的人对SOA不敏感。在目前的提案中，我们将对大约500名受试者进行心理物理筛查，以确定受影响的SOA不敏感的先证者和年龄、性别和种族匹配的未受影响的对照组。将对已确定的对SOA不敏感的先证者的大家庭进行检查。将进行相对风险比、家族相关性、隔离分析以及环境和病史访谈，以确定遗传性，如果是遗传的，遗传模式为SOA不敏感。这项研究还有一个优势，那就是检测了一种人类的表型，这种表型与已经很好描述的小鼠的SOA不敏感表型相似。将从所有受试者身上收集DNA样本，目的是对候选基因进行多态筛选，并对基因组的候选区域进行基于家族的连锁分析。作为第二个目标，将对5000名受试者进行筛查，以确定严重失明的流行率。这种新的表型需要广泛的分析，才能了解它对受影响个体的感知品味世界的影响。苦盲先证者和年龄、种族和性别匹配的正常对照组将在实验室进行更详细的心理生理表型分析。对这些重要味觉特征的分析有可能揭示味觉编码的组织原理以及潜在的味觉基因组学。

DESCRIPTION (provided by applicant): 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.