Genetics of white color and iridophoroma in “Lemon Frost” leopard geckos

Abstract

The squamates (lizards and snakes) are close relatives of birds and mammals, with more than 10,000 described species that display extensive variation in a number of important biological traits, including coloration, venom production, and regeneration. Due to a lack of genomic tools, few genetic studies in squamates have been carried out. The leopard gecko, Eublepharis macularius, is a popular companion animal, and displays a variety of coloration patterns. We took advantage of a large breeding colony and used linkage analysis, synteny, and homozygosity mapping to investigate a spontaneous semi-dominant mutation, “Lemon Frost”, that produces white coloration and causes skin tumors (iridophoroma). We localized the mutation to a single locus which contains a strong candidate gene, SPINT1, a tumor suppressor implicated in human skin cutaneous melanoma (SKCM) and over-proliferation of epithelial cells in mice and zebrafish. Our work establishes the leopard gecko as a tractable genetic system and suggests that a tumor suppressor in melanocytes in humans can also suppress tumor development in iridophores in lizards.

Chromatophoromas in Reptiles

“…Melanophoromas are often described as dark brown to black [ 8 , 9 , 12 , 13 , 24 ]. Iridophoromas are often described as white [ 8 , 9 , 25 ]. Xanthophoromas may be yellow, orange, or red [ 8 , 9 , 16 , 26 ].…”

“…A genetic predisposition to developing cutaneous and oral iridophoromas has been postulated in the “lemon frost” color variant of the leopard gecko ( Eublepharis macularius ) [ 25 , 32 ]. This population is highly inbred due to selective breeding for unique color variations, and has a high incidence of iridophoromas [ 25 , 32 ] ( Figure 2 a–d).…”

“…A genetic predisposition to developing cutaneous and oral iridophoromas has been postulated in the “lemon frost” color variant of the leopard gecko ( Eublepharis macularius ) [ 25 , 32 ]. This population is highly inbred due to selective breeding for unique color variations, and has a high incidence of iridophoromas [ 25 , 32 ] ( Figure 2 a–d). Guo et al, reported that 80% of the homozygous leopard geckos (from a large captive breeding colony) that had the lemon frost (lf) allele developed iridophoromas between 6 months to 5 years of age [ 25 ].…”

“…This population is highly inbred due to selective breeding for unique color variations, and has a high incidence of iridophoromas [ 25 , 32 ] ( Figure 2 a–d). Guo et al, reported that 80% of the homozygous leopard geckos (from a large captive breeding colony) that had the lemon frost (lf) allele developed iridophoromas between 6 months to 5 years of age [ 25 ]. They localized the mutation to a single locus containing a strong candidate gene, serine peptidase inhibitor, Kunitz type 1 (SPINT1) [ 25 ].…”

“…Guo et al, reported that 80% of the homozygous leopard geckos (from a large captive breeding colony) that had the lemon frost (lf) allele developed iridophoromas between 6 months to 5 years of age [ 25 ]. They localized the mutation to a single locus containing a strong candidate gene, serine peptidase inhibitor, Kunitz type 1 (SPINT1) [ 25 ]. SPINT1 is a tumor suppressor gene that has been implicated in the development of human cutaneous melanoma and unregulated proliferation of epithelial cells in mice and zebrafish [ 33 , 34 ].…”