EXPRESSION AND FUNCTION OF CONE PIGMENT GENES

描述(改编自申请者摘要)：长期目标是 了解基于视锥细胞的视觉分子遗传学 感光颜料。具体目标1将决定锥体之间的关系 X染色体上的感光基因和在视网膜中转录的基因。 基因组锥体光致变色基因的比较研究 人类视网膜中的感光色素信使RNA将为 了解是什么决定了哪些光色素基因被“开启”，以及 是什么控制着每个基因的表达水平。具体目标2 将描述锥体种群和色素mRNAs如何在 眼睛位于不同的视网膜位置，以及它们在不同个体之间的差异。 这些是了解治理机制的基本步骤 未分化细胞成为L锥体或M锥体的决定。 特指目标3将测试正常多态氨基酸的假设 以视锥为基础的视力障碍中的异常组合发生，并将 探索这种异常是否会导致这些疾病。色素基因 含有零星的核苷酸多态。这些指定了几个正常的 氨基酸替换以不同的组合出现在 颜料。单独来看，每种氨基酸的替代都是良性的。然而， 特定的mRNAs，可以指定特定的氨基酸组合 在人类视网膜中没有被检测到。然而，可以指定的基因 在基于视锥的视觉中，这些组合似乎发生频率很高 精神错乱。这表明，在这些疾病中，色素可能含有 特殊的氨基酸组合，不稳定并对人体产生不利影响 锥体功能或生存能力。

DESCRIPTION (Adapted from applicant's abstract): The long term goal is to understand the molecular genetics of vision that is based on cone photopigments. Specific aim 1 will determine the relationship between cone photopigment genes on the X-chromosome and those transcribed in the retina. A comparison of the genomic cone photopigment genes with the presence of photopigment messenger RNA in the human retina will provide a basis for understanding what determines which photopigment genes are "turned on" and what controls the level at which each gene is expressed. Specific aim 2 will characterize how the cone populations and the pigment mRNAs vary within an eye at different retinal locations and how they vary across individuals. These are essential steps toward understanding the mechanisms that govern the decision of an undifferentiated cell to become an L-cone or an M-cone. Specific aim 3 will test the hypothesis that normal polymorphic amino acids occur in abnormal combinations in cone-based vision disorders and will explore whether such abnormalities cause the disorders. The pigment genes contain scattered nucleotide polymorphisms. These specify several normal amino acid substitutions that occur in varied combinations among the pigments. Individually, each amino acid substitution is benign. However, specific mRNAs which would specify particular combinations of amino acids have not been detected in human retinas. However, genes that would specify those combinations appear to occur with high frequency in cone-based vision disorders. This suggests that, in these disorders, the pigment may contain particular amino acid combinations which are unstable and adversely affect cone function or viability.