HUMAN COLOR VISION--A MOLECULAR GENETIC ANALYSIS

所提出的研究是针对结构的定义， 人类的视觉色素，并试图了解这些 结构介导人类的颜色视觉。 更具体地说，我们希望测试 三种视锥细胞中的视色素类似于 视杆的rhodospin共价地由脱辅基蛋白（视蛋白）组成 与常见的11-顺式视网膜发色团有关， 视色素之间的吸收光谱是由结构 视蛋白之间的差异，这些结构差异是由 多基因家族成员间的核苷酸序列差异 编码视蛋白，而众所周知的颜色遗传变异 视觉是由编码视锥细胞视蛋白的那些成员的突变引起的。 为此，我们建议克隆，分离和测序的基因， 编码人类视色素的蛋白质部分， 和突变个体。 从这些克隆的基因中， 在适当的宿主-载体系统中编码蛋白质，将它们附着在 11-cis retinal，并在体外研究重建的视色素。 这 这种方法应该允许对模型进行直接测试。 详细分析 许多突变体应该提供对分子结构的了解， 视觉色素的作用机制，这对我们的 对视觉及其病理异常有基本的了解。 我们 策略是（i）在核苷酸水平上分离和表征 基因编码的最好的研究视觉色素，牛rhodospin（ii）使用 从该基因的编码序列作为杂交探针分离至少 人视蛋白基因之一（例如，对于人的视紫红质）， 基因组DNA克隆文库，和（iii）类似地使用这样的人基因 分离以鉴定和分离假定视蛋白的其他成员 人类的多基因家族 这个计划的第一步是 完成了

The proposed research is directed toward a definition of the structure of the human visual pigments and toward an understanding of how these structures mediate human color vision. More specifically, we wish to test the model that the visual pigments in the three types of cones resemble the rhodospin of the rods in consisting of an apoprotein (opsin) covalently linked to the common 11-cis retinal chromophore, that differences in the absorption spectra among the visual pigments result from structural differences among the opsins, that those structural differences result from nucleotide sequence differences among the members of a multigene family encoding the opsins, and that the well known genetic variations in color vision result from mutations in those members that encode the cone opsins. To this end, we propose to clone, isolate and sequence the genes that encode the protein moieties of the human visual pigments fom both normal and mutant individuals. From these cloned genes we will produce the encoded proteins in appropriate host-vector systems, attach them to the 11-cis retinal and study the reconstituted visual pigments in vitro. This approach should allow a direct test of the model. Detailed analyses of many mutants should provide insights into the molecular structure and mechanism of action of the visual pigments that are important both to our basic understanding of vision and to its pathologic anomalies. Our strategy is (i) to isolate and characterize at the nucleotide level the gene encoding the best studied visual pigment, bovine rhodospin (ii) to use coding sequences from this gene as hybridization probes to isolate at least one of the human opsin genes ( e.g., that for human rhodopspin) from a library of genomic DNA clones, and (iii) to similarly use such a human gene isolate to identify and isolate other members of the postulated opsin multigene family in humans. The first step in this plan has been acccomplished.