EXPRESSION AND FUNCTION OF CONE PIGMENT GENES

描述（改编自申请人的摘要）：长期目标是 理解视觉的分子遗传学， 颜料。 具体目标1将确定锥之间的关系 X染色体上的色素基因和在视网膜中转录的色素基因。 基因组视锥细胞色素基因的比较， 人类视网膜中的色素信使RNA将为 了解是什么决定了哪些色素基因被“打开”， 是什么控制着每个基因的表达水平 具体目标2 将表征视锥细胞群和色素mRNA在细胞内的变化， 一只眼睛在不同的视网膜位置，以及它们如何在个体之间变化。 这些都是理解这些机制的基本步骤， 决定一个未分化的细胞成为L-视锥或M-视锥。 具体目标3将检验正常多态性氨基酸 在视锥细胞性视觉障碍中以异常组合发生， 探索这些异常是否会导致这些疾病。 色素基因 含有分散的核苷酸多态性。 这些规定了几个正常的 氨基酸取代以不同的组合发生在这些氨基酸之间， 颜料. 单独地，每个氨基酸取代都是良性的。 然而，在这方面， 特定的mRNA可以指定特定的氨基酸组合 还没有在人类视网膜中检测到。 然而，基因会指定 这些组合在视锥细胞视觉中出现的频率很高 紊乱 这表明，在这些疾病中，色素可能含有 不稳定的和不利影响的特定氨基酸组合 视锥功能或生存能力。

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.