title: Analysis of introns and promoters of L/M visual pigment genes in relation to deutan color-vision deficiency with an array of normal gene orders.
abstract: Among the 447 Japanese men with deutan color-vision deficiency that we analyzed, 61 had a normal order array of L/M pigment genes. Three of the 61 men had an exonic mutation, but the other 58 had no mutations even in the flanking introns of their M genes. In these 58 men, 55 had a -71A --> C substitution in the M gene. Two hypotheses were built up for the substitution: it is in linkage disequilibrium with a genuine cause of deficiency in the introns, or itself is the cause of the deficiency. For the first hypothesis, we sequenced entire regions of both the L and M genes in 30 color-normal Japanese men who had one each of the L and M genes to understand normal variations of the introns. Fifty-two already known and 15 newly identified polymorphic sites could be classified into three categories: those with no polymorphisms in the Japanese group, those essentially different between the L and the M genes, and the others. We then sequenced the entire region of the M genes in 12 representative deutan individuals with a normal gene-order array but found no significant mutations. For the second hypothesis, we performed a reporter assay and found that the M gene promoter with -71C had a 60-70% reduction in activity when compared to that with -71A. These results suggest that the -71A --> C substitution is not in linkage disequilibrium with an intronic mutation, but the substitution itself may affect the transcription of the M gene, leading to deutan deficiency.
authors: Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Seta, Otsu, Japan. datt@belle.shiga-med.ac.jp
authors: Hisao
authors: H
authors: Ueyama
authors: Shoko
authors: S
authors: Tanabe
authors: Sanae
authors: S
authors: Muraki-Oda
authors: Shinichi
authors: S
authors: Yamade
authors: Masahito
authors: M
authors: Ohji
authors: Iwao
authors: I
authors: Ohkubo
mesh_terms: D016022:Case-Control Studies; D003117:Color Vision Defects / Q000235:genetics*; D055358:Cone Opsins / Q000235:genetics*; D023061:Gene Order / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D055358:Cone Opsins