Categories: Vision / eye phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 204000 (trait)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 1998

Species-specific name: GUCY1*

Species-specific symbol: Initially rc or rd; since 1999 the official symbol is GUCY1*

Species-specific description: This disorder is associated with a deficiency of guanylate cyclase activating protein-2 (GCAP2), resulting in abnormal activation of guanylate cyclase in photoreceptors, which in turn results in low levels of cGMP and an absence of phototransduction (Semple-Rowland et al. (1996). This deficiency is due to a null mutation in guanylate cyclase (Semple-Rowland et al., 1998)

History: The mutation was first reported by Cheng et al. (1980), then at the University of Minnesota, who gave it the symbol "rc" (for rod-cone absent). Noting that the disorder is actually characterised by photoreceptor cells that are normal at hatching but which degenerate with age, Ulshafer et al. (1984)(University of Florida) renamed the mutation "rd". These two symbols have been used in the literature. As explained by Semple-Rowland and Cheng (1999), Cheng moved his "rc" colony to the University of British Columbia in Vancouver in 1981; and also in the early 1980s, an "rd" colony was established at the University of Florida from a sample of Minnesota "rc" birds.

Inheritance: Cheng et al. (1980) provided evidence of autosomal recessive inheritance.

Molecular basis: By cloning and sequencing a very likely candidate gene on the basis of the physiology and biochemistry of the disorder in chickens, and on the homologous disorder in humans, Semple-Rowland et al. (1998) cloned and sequenced the chicken photoreceptor guanylate cyclase gene, and identified the causative mutation as an indel in that gene, resulting in a peptide that "is predicted to lack the membrane-spanning domain and the regions immediately flanking it, a region essential for proper folding and enzyme activity".

Semple-Rowland and Cheng (1999) showed that "both the rd and rc chickens carry the same GC1 null mutation", and proposed replacing the symbols "rd" and rc" with GUCY1*.

Associated gene: