title: The molecular basis of dichromatic color vision in males with multiple red and green visual pigment genes.
abstract: We investigated the genotypic variation in 50 red-green color vision deficient males (27 deuteranopes and 23 protanopes) of middle European ancestry who possess multiple genes in the X-linked photopigment gene array. We have previously shown that only the first two genes of the array are expressed and contribute to the color vision phenotype. Therefore, the hypothesis is that the first two genes possessed by multigene-dichromats encode pigments of identical or nearly identical spectral sensitivity: one gene normal (R or G) and the other a hybrid (G/R or R/G). The spectral sensitivities of the encoded pigments were inferred from published in vitro and in vivo data. The color vision phenotype was assessed by standard anomaloscopy. Most genotypes (92%) included hybrid genes whose sequence and position and whose encoded pigment correlated exactly with the phenotype. However, one and possibly two of the protanopes had gene arrays consistent with protanomaly rather than protanopia, since two spectrally different pigments may be encoded by their arrays. Two of the deuteranopes had only R- and G-photopigment genes, without any detectable G/R-hybrid genes or any as-of-yet identified point mutation or coding/promoter sequence deletions. Further, an unexpectedly high number of multigene-deuteranopes (11%) had the C203R mutation in their most upstream G-pigment gene, suggesting a founder effect of middle European origin for this mutation. About half of the protanopes possessed an upstream R/G-hybrid gene with different exon 2 coding sequences than their downstream G-pigment gene(s), which is inconsistent with published data implying that a single amino acid substitution in exon 2 can confer red-green color discrimination capacity on multigene-protans by altering the optical density of the cones.
authors.affiliation: Department of Neuro-Ophthalmology, University Eye Hospital, Roentgenweg 11, D-72076 Tübingen, Germany.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Jagla
authors.forename: Herbert
authors.initials: H
authors.lastname: Jägle
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.forename: Lindsay T
authors.initials: LT
authors.lastname: Sharpe
authors.forename: Samir S
authors.initials: SS
authors.lastname: Deeb
mesh_terms: D003118:Color Perception / Q000235:genetics*; D003117:Color Vision Defects / Q000235:genetics* / Q000503:physiopathology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005091:Exons; D005136:Eye Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D005810:Multigene Family; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics; D011995:Recombination, Genetic; D015183:Restriction Mapping; D012160:Retina / Q000502:physiology*; D012168:Retinal Pigments / Q000235:genetics*; D017299:Rod Opsins; D014960:X Chromosome / Q000235:genetics
chemical_list: D005136:Eye Proteins; D012168:Retinal Pigments; D017299:Rod Opsins; C095855:long-wavelength opsin; C095854:middle-wavelength opsin; D004247:DNA