Genetics Of White Color And Iridophoroma In "Lemon Frost" Leopard Geckos

Author summary The squamates (lizards and snakes) comprise a diverse group of reptiles, with more than 10,000 described species that display extensive variation in a number of important biological traits, including coloration. In this manuscript, we used quantitative genetics and genomics to map the mutation underlying white coloration in the Lemon Frost morph of the common leopard gecko, Eublepharis macularius. Lemon Frost geckos have increased white body coloration with brightened yellow and orange areas. This morph also displays a high incidence of iridophoroma, a tumor of white-colored cells. We obtained phenotype information and DNA samples from geckos in a large breeding colony and used genome sequencing and genetic linkage analysis to localize the Lemon Frost mutation to a single locus. This locus contains a strong candidate gene, SPINT1, a tumor suppressor implicated in human skin cutaneous melanoma. Together with other recent advances, our work brings reptiles into the modern genetics era.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.