HUMAN BITTER TASTE: GENETICS OF PSYCHOLOGICAL TRAITS

描述（由申请人提供）：对于一般的感觉科学，一个主要目标是了解不同层次的感知和潜在感觉机制之间的关系；也就是说，将心理后果归因于与感觉系统相关的基因的功能。仅在苦味中，就有几十个基因专门与感知苦味有关。将这些基因的功能归因于这些基因的艰巨任务将需要多学科方法，将遗传学和基因组学与感知和生理学研究结合起来。该项目的最终长期目标是确定与特定苦味敏感性相关的基因。正如本提案中概述的那样，实现目标的基本初始步骤是对苦味感知进行表型分析，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，以检查许多苦涩的感知属性。我们现在已经确定了两类对苦味敏感的个体差异：(i)对八乙酸蔗糖（SOA）表现出特定的苦味不敏感的人；（ii）对其他味觉正常的人完全没有苦味。苦盲是一种罕见的特征，目前只在三个个体中发现。大约30%的人对SOA不敏感。在目前的建议中，我们将对大约500名受试者进行心理物理筛选，以确定受影响的soa不敏感先证者和年龄，性别和种族匹配的未受影响的对照组。将检查已确定的soa不敏感先证者的大家庭。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SOA不敏感的遗传能力，如果是遗传的，则确定遗传模式。SOA研究还具有检查人类表型与小鼠SOA不敏感表型相似的优点。将收集所有受试者的DNA样本，目的是筛选候选基因的多态性，并对候选基因组区域进行基于家族的连锁分析。作为第二个目标，将筛选5000名受试者，以确定苦盲的患病率。这种新的表型将需要广泛的分析，以了解其对受影响个体的感知味觉世界的影响。苦盲先证者与年龄、种族和性别匹配的正常对照将在实验室中进行更详细的心理物理表型分析。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.