GENES AND VISUAL PIGMENTS OF RED GREEN COLOR VISION

红绿色视觉的基因和视觉色素

• 批准号: 2888388
• 负责人: MAUREEN E NEITZ
• 金额: $ 22.79万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888388
• 关键词: clinical research; color blindness; color visions; cone cell; electroretinography; gene expression; gene rearrangement; genotype; human genetic material tag; human subject; male; molecular cloning; molecular genetics; nucleic acid sequence; nucleic acid structure; phenotype; point mutation; polymerase chain reaction; rhodopsin; sex linked trait; southern blotting; visible light; vision disorders; visual pigments

The long term goal of this research is to understand the molecular genetics of vision based on cone photopigments. To achieve this goal, we must first establish a relationship between color vision phenotype and genotype. This requires a clear, accurate understanding of the genotype. Recent evidence indicates that the structure of the arrays underlying normal color vision are radically different than previously appreciated. Thus, the immediate goal of the work proposed here is to gain understanding of the structure of the X-linked pigment gene array. What are the numbers and rations of pigment genes in individual arrays, how do the numbers vary, and what role do "extra" pigment genes in play in normal vision and in vision abnormalities? What recombination mechanisms play a role in altering the structure of the array; which alterations are associated with color vision defects and more serious vision disorders? How are individual differences in the amino acids of the opsins related to pigment function; what changes are associated with color vision defects, or other vision disorders? Each of the specific aims of this proposal builds on a different new discovery from our laboratories. Each discovery has far reaching implications for understanding vision based on these genes. 1) We have evidence that some individuals do not have intact middle-wave genes, but instead have incomplete genes. 2) We have evidence that individual differences in the numbers and ratios of genes that underlie normal color vision are far greater than had been imagined. 3) We identified a mutation in the genes underlying protanomalous color vision that does not change the absorption peak of the pigment, yet it alters pigment function to produce the difference between anomalous trichromacy and dichromacy. Toward exploring the implications of these findings the specific aims of our research are: 1) To investigate gene rearrangements among the X- linked visual pigment genes with regard to the frequency of occurrence of incomplete middle- or long-wave genes in normal vision and vision defects, and the genetic mechanisms that produce the deletions. 2) To characterize the basic structure of the X-linked visual pigment gene array with regard tot he number and ration of long- and middle-wave genes in the arrays of observers with normal color vision and those with color vision defects. 3) To characterize athe pigments underlying the color vision defects, protanopia and protanomaly, with regard to spectral sensitivity, optical density, and bleaching and regeneration kinetics, and to explore the relationship between gene sequence differences and these functional differences in encoded pigments. Visual capacities of males with normal and defective color vision will be examined in detail using psychophysical methods and the electroretinogram. The X-linked pigment genes will be investigated using Southern analysis, the polymerase chain reaction,a nd DNA sequence analysis.

这项研究的长期目标是了解 基于视锥细胞色素的视觉遗传学。 为了实现这一目标，我们 必须首先建立色觉表型和 基因型 这需要对基因型有一个清晰、准确的理解。 最近的证据表明， 正常的色觉与以前认识到的完全不同。 因此，这里提出的工作的直接目标是获得理解 X连锁色素基因阵列的结构。 数字是多少 和色素基因在单个阵列中的比例，这些数字是如何变化的， 以及“额外”色素基因在正常视觉和 视力异常 什么样的重组机制在 改变阵列的结构;这些改变与 色觉缺陷和更严重的视觉障碍？ 个人如何 与色素功能相关的视蛋白氨基酸的差异; 什么变化与色觉缺陷或其他视觉有关 精神障碍 该提案的每一个具体目标都建立在一个不同的新目标之上。 我们实验室的发现。 每一个发现都具有深远的意义 这些基因对理解视觉的影响。1)我们有 有证据表明，有些人没有完整的中波基因，但 而是不完整的基因。 2)我们有证据表明 正常颜色基因的数量和比例差异 远比想象的要伟大。 3)我们确定了一个 色觉异常的基因突变， 改变了色素的吸收峰，但也改变了色素的功能 来区分异常三色视觉和正常三色视觉。 为了探索这些发现的影响， 我们的研究内容是：1）研究X染色体的基因重排， 连锁的视觉色素基因的发生频率， 在正常视力和视力缺陷中不完全的中或长波基因， 以及产生缺失的遗传机制。 2)表征 X连锁视色素基因阵列的基本结构， 结果表明，在基因芯片中，长波基因和中波基因的数目和比例均为0. 色觉正常和色觉缺陷的观察者。 第三章 为了表征色觉缺陷背后的色素沉着， 就光谱敏感性而言， 密度，漂白和再生动力学，并探讨 基因序列差异与这些功能之间的关系 编码色素的差异。 色觉正常和色觉有缺陷的男性的视觉能力将 使用心理物理学方法和视网膜电图进行详细检查。 X连锁色素基因将使用Southern分析进行研究， 聚合酶链反应和DNA序列分析。