HUMAN BITTER TASTE: GENETICS OF PSYCHOLOGICAL TRAITS

人类苦味：心理特征的遗传学

• 批准号: 6757162
• 负责人: Paul A. S Breslin
• 金额: $ 32.57万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757162
• 关键词: clinical research; family genetics; genetic disorder diagnosis; genetic polymorphism; genetic screening; genetic susceptibility; human genetic material tag; human population study; human subject; interview; linkage mapping; longitudinal human study; mass screening; molecular biology information system; nucleic acid purification; phenotype; polymerase chain reaction; pseudogenes; psychophysics; questionnaires; sensory discrimination; sensory disorder diagnosis; sensory signal detection; sucrose; taste

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.

描述（由申请人提供）：对于一般的感觉科学来说，一个主要目标是理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，就有数十个专门与检测苦味相关的基因。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将遗传学和基因组学与感知和生理学研究相结合的多学科方法。该项目的最终长期目标是识别与特定苦味敏感性相关的基因。正如本提案中概述的，实现目标的一个重要的第一步是对苦味感知进行表型分析并严格建立可靠的个体差异。将使用广泛的强制选择和缩放技术来筛选受试者，这些技术会检查许多痛苦的感知属性。我们现在已经确定了苦味敏感性方面存在两类明显的个体差异：（i）对蔗糖八乙酸酯（SOA）表现出特定的苦味不敏感性的人，以及（ii）完全苦味盲但味觉正常的人。苦涩失明是迄今为止在三人身上发现的一种罕见特征。大约 30% 的人普遍对 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学筛查，以确定受影响的 SOA 不敏感先证者以及年龄、性别和种族匹配的未受影响的对照。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 不敏感性的遗传性以及遗传模式（如果是遗传性的）。 SOA 研究还具有检查人类表型的优点，该表型与已明确表征的小鼠 SOA 不敏感表型相似。将从所有受试者收集 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。第二个目标是对 5000 名受试者进行筛查，以确定苦涩盲症的患病率。这种新颖的表型需要进行广泛的分析，以了解其对受影响个体的感知味觉世界的影响。苦涩盲先证者和年龄、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学表型分析。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。