MOLECULAR GENETICS OF COLOR VISION

色觉的分子遗传学

• 批准号: 6329521
• 负责人: SAMIR Sami DEEB
• 金额: $ 27.85万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6329521
• 关键词: African American; DNA binding protein; Japanese; animal genetic material tag; caucasian American; color blindness; color visions; cone cell; electroretinography; fluorescent in situ hybridization; gel mobility shift assay; gene expression; gene mutation; genetic polymorphism; genetically modified animals; human genetic material tag; human subject; laboratory mouse; molecular cloning; molecular genetics; northern blottings; polymerase chain reaction; racial /ethnic difference; sex linked trait; transcription factor; visual pigments

The central objective of this proposal is to define the molecular genetics of red/green color vision by relating the molecular genetics of the X- linked photopigment genes to their expression in the retina and to the color vision phenotype. The red and green pigment genes are arranged in an array on the X-chromosome consisting of a single red and one or more green pigment genes. Deletion of genes or formation of hybrid genes (red-green and green-red) due to illegitimate recombination at this locus causes color vision defects. However, not all other gens of the red/green array are expressed in the retina, creating uncertainties in predicting color vision phenotype from genotype. Understanding the mechanism by which selective expression of these genes is accomplished is fundamental to defining genotype-phenotype relationships. We have delineated critical regulatory regions of the red-green gene locus and detected proteins that bind to them. A major aim of this proposal is to clone and character the transcription factors that play major roles in regulating expression of the visual pigment genes. We will map the genes encoding these factors on human and mouse chromosomes. Map positions will be correlated with known loci associated with retinal diseases. We developed a rapid method for determining gene order in males who have up to three pigment genes in their arrays and found evidence for a role of gene order in gene expression and color vision. We propose to advance their method in order to determine gene order in the majority of individuals. Knowing the sequence and gene order will allow more precise prediction of the spectral sensitivities of clones and the color vision phenotype. The ratio of red to green cones was determined indirectly by measuring relative levels of mRNA in postmortem human retinae. We propose to determine the ratio and distribution of cones in the retina directly by in situ molecular techniques. The findings will be of fundamental importance for the visual sciences. We observed a very high frequency of green-red hybrid genes among Africans. We will investigate the sequence of these hybrids and determine their position in the array. Elucidation of the molecular mechanism of expression of this locus affecting sensory perception is a model for expression of genes in other complex loci. These studies may lead to rapid and accurate blood tests for color vision defects. The novel photoreceptor-specific genes we propose to clone may be good candidates for some of the inherited retinal diseases.

这一建议的中心目标是通过将X连锁光色素基因的分子遗传学与它们在视网膜中的表达以及与色觉表型之间的关系来定义红色/绿色视觉的分子遗传学。红色和绿色色素基因在X染色体上排列成阵列，由单个红色和一个或多个绿色色素基因组成。由于该基因座的非法重组导致基因缺失或形成杂交基因(红-绿和绿-红)，会导致色觉缺陷。然而，并不是所有红/绿阵列的其他基因都在视网膜中表达，这给从基因预测色觉表型带来了不确定性。了解这些基因选择性表达的机制是确定基因-表型关系的基础。我们已经描绘了红色-绿色基因位点的关键调节区，并检测到了与它们结合的蛋白质。这项建议的一个主要目的是克隆和鉴定在调节视觉色素基因表达方面起主要作用的转录因子。我们将把编码这些因子的基因定位在人类和小鼠的染色体上。MAP的位置将与与视网膜疾病相关的已知基因相关联。我们开发了一种快速方法来确定在其阵列中有多达三个色素基因的男性的基因顺序，并发现了基因顺序在基因表达和颜色视觉中的作用的证据。我们建议改进他们的方法，以确定大多数个体的基因顺序。了解序列和基因顺序将允许更准确地预测克隆的光谱敏感度和颜色视觉表型。通过测量人死后视网膜的相对mRNA水平，间接确定红色视锥与绿色视锥的比例。我们建议用原位分子技术直接测定视锥细胞在视网膜中的比例和分布。这一发现将对视觉科学具有根本性的重要性。我们观察到非洲人中绿色和红色杂交基因的频率非常高。我们将调查这些杂交体的序列并确定它们在阵列中的位置。阐明该基因表达影响感官知觉的分子机制是研究其他复杂基因表达的一个模型。这些研究可能导致对色觉缺陷的快速准确的血液测试。我们计划克隆的新的光感受器特异性基因可能是一些遗传性视网膜疾病的很好候选基因。