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感知之间的关系和不同层次的潜在感觉机制;也就是说，将心理后果分配给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参与检测苦味。将功能归于这些基因的艰巨任务将需要多学科的方法，将遗传学和基因组学与感知和生理学的研究相结合。该项目的最终长期目标是确定与特定味觉敏感性相关的基因。如本提案所述，实现目标的一个重要的初始步骤是表型苦味感知并严格建立可靠的个体差异。受试者将使用广泛的强迫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苦味敏感性的两种强大的个体差异：（i）对蔗糖八乙酸酯（SOA）表现出特定苦味不敏感性的人和（ii）完全苦味盲的人，否则味觉正常。到目前为止，苦盲症是在三个个体中发现的罕见特征。SOA不敏感性出现在大约30%的人群中。在本研究中，我们将对大约500名受试者进行精神障碍筛查，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。将对已确定的SOA不敏感先证者的大家族进行检查。将进行相对风险比、家族相关性、分离分析以及环境和病史访谈，以确定SOA不敏感性的遗传性，如果是遗传性的，还将确定SOA不敏感性的遗传模式。SOA研究还具有检查与良好表征的小鼠SOA不敏感表型相似的人类表型的优点。将从所有受试者中采集DNA样本，目的是筛选候选基因的多态性，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，将筛选5000名受试者，以确定苦盲症的患病率。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。将在实验室中更详细地对盲先证者和年龄、种族和性别匹配的正常对照进行精神病表型分型。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.