Position of a 'green-red' hybrid gene in the visual pigment array determines colour-vision phenotype

The X-linked red- and green-pigment genes are arranged in a head-to-tail ta ndem array(1-3). The colour-vision defect of deuteranomaly (in 5% of males of European descent) is associated with a 5'-green-red-3' visual-pigment hy brid gene(4,5), which may also exist in males with normal colour vision(5-7 ). To explain why males with a normal red, a normal green and a green-red h ybrid gene may have either normal or deutan colour vision, we hypothesized that only the first two genes are expressed(8,9) and deuteranomaly results only if the green-red hybrid gene occupies the second position and is expre ssed preferentially over normal green-pigment genes occupying more distal p ositions. We used long-range PCR amplification and studied 10 deutan males (8 deuteranomalous and 2 deuteranopic) with 3 visual pigment genes (red, gr een and green-red hybrid) to investigate whether position of the hybrid gen e in the array determined gene expression. The green-red hybrid gene was al ways at the second position land the first position was always occupied by the red gene). Conversely, in two men with red, green and green-red hybrid genes and normal colour vision, the hybrid gene occupied the third position . When pigment gene mRNA expression was assessed in post-mortem retinae of three men with the red, green and green-red genotype, the green-red hybrid gene was expressed only when located in the second position. We conclude th at the green-red hybrid gene will only cause deutan defects when it occupie s the second position of the pigment gene array.