MOLECULAR GENETIC STUDIES OF HUMAN COLOR VISION

红色或绿色色觉缺陷（“色盲”）是最常见的色觉缺陷之一。 在人群中常见的遗传变异，影响高达10%的男性。 色觉缺陷的分子遗传学研究进展， 表明这是由于X染色体上的视色素基因缺失引起的 染色体或从存在的融合基因的编码视觉 具有反常吸收波长的色素。加上 发现绿色视色素基因的拷贝数是多态的， 这些观察结果表明， X染色体上的基因座是反复不等重组的靶。 为了研究这种遗传变异的分子基础，我们建议 检查正常男性的视觉色素位点的组织， 色觉者（三色视者）以及那些有色觉的人 缺陷色觉将通过使用分析测试进行严格测试。 异常镜基因定位研究将通过常规方法进行。 Southern印迹和场反转凝胶电泳。的基因 已通过放射自显影的密度测定法进行定量， 通过测量NotI限制性片段的大小确认的数量 包含了整个视觉色素基因复合体的基因间 红色和绿色之间以及绿色和绿色之间的视色素区域 基因将被克隆和绘制，以确定它们在哪里产生了分歧。我们 将利用这些DNA侧翼序列来绘制另一个 色觉正常且基因拷贝数为R：G 1：1的受试者， 1：2的比例来确定这些基因中可能存在的遗传变异程度。 个体，并确定重组的位点， 基因拷贝数多态性。我们将建立基因组织 视觉色素缺乏的个体，并将绘制潜在的网站 在色觉缺陷的个体中的重组。这些网站 将进行测序以确定它们是否具有共同的结构特征 或与先前重组的其他“热点” 在基因组中识别。我们预计这些研究将产生 深入了解不平等重组如何有助于发展 遗传缺陷

Red or green color vision deficiency ("color blindness") is one of the most common genetic variants in the population, affecting up to 10% of males. Recent studies about the molecular genetics of color vision deficiency, suggest that this arises from deletion of the visual pigment genes on the X chromosome or from the presence of fusion genes which code for visual pigments having anomalous wavelengths of absorption. Coupled with the finding that copy number of the green visual pigment gene is polymorphic in the population, these observations would suggest that the visual pigment loci on the X chromosome are a target for recurrent unequal recombination. To study the molecular basis of this genetic variation, we propose to examine the organization of the visual pigment loci in males with normal color vision (trichromats) as well as those who have color vision deficiency. Color vision will be rigorously tested by use of an analytical anomaloscope. Gene mapping studies will be performed by conventional Southern blotting and by field inversion gel electrophoresis. Genes that have been quantified by densitometry of autoradiograms, will have the copy number confirmed by measuring the size of the NotI restriction fragment that contains the entire visual pigment gene complex. The intergenic regions between red and green and between green and green visual pigment genes will be cloned and mapped to determine where they have diverged. We will use these DNA flanking sequences to map the genomes of the other subjects with normal color vision and with gene copy numbers of R:G 1:1 and 1:2 to establish the degree of genetic variability that may exist in these individuals and to identify the sites of recombination that gave rise to the gene copy number polymorphisms. We will establish the gene organization of individuals with visual pigment deficiency and will map potential sites of recombination in individuals with color vision deficiency. These sites will be sequenced to determine whether they have common structural features among themselves or with other "hot spots" of recombination previously identified in the genome. We anticipate that these studies will yield insight into how unequal recombination contributes to the development of genetic defects.