Genetic variants in melanogenesis proteins TYRP1 and TYR are associated with the golden rhesus macaque phenotype

Abstract Nonhuman primates (NHPs) are vital translational research models due to their high genetic, physiological, and anatomical homology with humans. The “golden” rhesus macaque (Macaca mulatta) phenotype is a naturally occurring, inherited trait with a visually distinct pigmentation pattern resulting in light blonde colored fur. Retinal imaging also reveals consistent hypopigmentation and occasional foveal hypoplasia. Here, we describe the use of genome-wide association in 2 distinct NHP populations to identify candidate variants in genes linked to the golden phenotype. Two missense variants were identified in the Tyrosinase-related protein 1 gene (Asp343Gly and Leu415Pro) that segregate with the phenotype. An additional and distinct association was also found with a Tyrosinase variant (His256Gln), indicating the light-colored fur phenotype can result from multiple genetic mechanisms. The implicated genes are related through their contribution to the melanogenesis pathway. Variants in these 2 genes are known to cause pigmentation phenotypes in other species and to be associated with oculocutaneous albinism in humans. The novel associations presented in this study will permit further investigations into the role these proteins and variants play in the melanogenesis pathway and model the effects of genetic hypopigmentation and altered melanogenesis in a naturally occurring nonhuman primate model. Peterson et al. describe the first genetic mapping of the “golden” rhesus macaque phenotype, a naturally occurring pigmentation trait. Using independent analyses of macaques at two different US Primate Research Centers the authors were able to attribute the phenotype to 3 different variants in the TYRP1 and TYR genes. They highlight the use of the macaque Genotype and Phenotype (mGAP) Resource to identify the genetic basis for the trait and its applicability as a non-human primate genetic model for oculocutaneous albinism.