GENES AND VISUAL PIGMENTS OF RED-GREEN COLOR VISION

我们的大部分日常活动是在光线水平下进行的，那里的视觉是基于视锥体光感受器的。基于视锥的视觉的一个特点是能够看清颜色。颜色是我们用眼睛收集的信息的一个重要组成部分；我们如此自动地使用颜色，以至于我们没有意识到它有多重要。它作为一种非语言代码，为我们提供关于我们周围世界的即时信息。常见的色觉遗传变异提供了一个独特的系统来研究视锥细胞马赛克的改变对视觉功能的影响，以及视锥细胞视蛋白氨基酸序列的变异如何影响视锥细胞的光感受器功能。这项研究的长期目标是了解视锥细胞视觉的分子遗传学，并了解基因和表型之间的关系。这项工作的一个实际应用是开发一种基因测试，以区分遗传性色觉缺陷和因疾病或接触有毒化学品或药物而获得的继发性色觉丧失。其具体目的是：1)确定L：M视锥比在正常肤色人群中的变异分布，并确定X染色体视色素基因座决定L：M视锥比的程度。2)研究X编码锥体色素初级氨基酸序列的自然差异对功能的影响，特别是锥体光谱灵敏度和光密度的变化。3)研究色觉缺陷背后的特定表型/基因型关系，涉及a)锥体色素有害突变在视力障碍中的作用；b)Protan色觉缺陷严重程度变化的分子基础；以及c)具有非常轻微缺陷但外观正常的色素基因阵列的男性和表现出色觉异常的女性携带者色觉丧失的分子遗传学基础。为了实现这些目标，我们将采取多学科方法，使用心理物理、电生理和分子生物学技术。

Most of our daily activities are performed at light levels where vision is based on cone photoreceptors. A feature of cone-based vision is the capacity to see in color. Color is an important component of the information that we gather with our eyes; we use color so automatically that we fail to appreciate how important it is. It serves as a non-linguistic code that gives us instant information about the world around us. Common inherited variations in color vision provide a unique system in which to study the effects of alterations in the cone mosaic on visual function and how a variation in the amino acid sequence of the cone opsin affects cone photoreceptor function. The long-term goals of the proposed research are to understand the molecular genetics of cone-based vision, and to understand the relationship between genotype and phenotype. A practical application of this work is the development of a genetic test to distinguish between inherited color vision deficiencies, and color vision loss acquired secondary to disease or exposure to toxic chemicals or drugs. The specific aims are: 1) To determine the distribution of variation in the L:M cone ratio in the color normal population and to determine the extent to which the L:M cone ratio is specified by the X-chromosome visual pigment gene locus. 2) To investigate the effects of naturally occurring differences in primary amino acid sequence of X-encoded cone pigments on function, specifically with regard to alterations in cone spectral sensitivity and optical density. 3) To investigate specific phenotype/genotype relationships underlying color vision deficiencies with regard to a) the role of deleterious mutations in cone pigments in vision disorders; b) the molecular basis for variation in the severity of protan color vision defects; and c) the molecular genetic basis for color vision loss in males with a very mild defect but with normal looking pigment gene arrays, and females carriers who exhibit color vision abnormalities. To achieve these goals we will take a multidisciplinary approach, using psychophysical, electrophysiological and molecular biological techniques.