In other species: Japanese medaka , dark-spotted frog , Japanese wrinkled frog , Tufted capuchin , hamadryas baboon , dog , red fox , domestic ferret , domestic cat , lion , humpback whale , ass (donkey) , pig , red deer , American bison , taurine cattle , rabbit , golden hamster , Mongolian gerbil , domestic guinea pig , Japanese ratsnake , water buffalo , four-striped grass mouse , ocelot gecko , American mink , Japanese raccoon dog , Rice frog

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 203100 (trait) , 606952 (trait) , 606933 (gene)

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: 2000

Cross-species summary: Congenital lack of pigment in most parts of the body. Due to a non-functional form of the enzyme tyrosinase. Also known as Oculocutaneous albinism (OCA), Acromelanism and as the Himalayan coat-colour pattern

Species-specific name: Variants in the TYR gene cause 'albino' as well as 'golden or blond' coat colour

Molecular basis: Ding et al. (2000): "Sequence analysis of the tyrosinase (TYR) coding region from one albino rhesus monkey (Macaca mulatta) family revealed that the two monkeys with phenotype similar to human TYR-negative oculocutaneous albinism (OCA) were homozygous for a missense mutation (S184TER) in exon 1 at codon 184." Wu et al. (2020) "identified [six] rhesus macaque models with clinical characteristics consistent with those of OCA patients according to observations of ocular behavior, fundus examination, and optical coherence tomography. Genomic sequencing revealed a biallelic p.L312I mutation in TYR and a homozygous p.S788L mutation in OCA2 [see OMIA:002130-9544 for inforamtion relating to the OCA2 variant], both of which were further confirmed to affect melanin biosynthesis via in vitro assays . ... all [six] of these albino monkeys carried [the] homozygous missense mutation, c.2363C>T, in the OCA2 gene. Additionally, three albino subjects ..., were found to exhibit a homozygous missense mutation, c.934C>A, in the TYR gene." Peterson et al. (2023) “used independent GWAS analysis of two rhesus macaque populations to attribute the genetic basis for the golden rhesus macaque phenotype to variants in the TYRP1 and TYR genes. … Two missense variants were identified in the Tyrosinase-related protein 1 (TYRP1) gene (Asp343Gly and Leu415Pro) that segregate with the phenotype [see OMIA:001249-9544 for details on the TYRP1 variants]. An additional and distinct association was also found with a Tyrosinase (TYR) variant (His256Gln), indicating the light-colored fur phenotype can result from multiple genetic mechanisms. ... While variant prediction algorithms predicted only mild effects from the [TYR] substitution (SIFT=0.05; PolyPhen=.533; CADD=8.802), the variant affects the same amino acid as a known pathogenic human allele linked to OCA1 (TYR p.His256Tyr; rs61754370 ... ).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Clinical features: Ding et al. (2000) report two "albino rhesus monkeys ... , with phenotype similar to human classic features of type 1A OCA, [who] lacked detectable melanin pigment ... . Their hair, skin, and fingernails were white, irides were pale blue and transilluminated completely, and their retinaes were unpigmented. They had greatly decreased visual acuity, foveal hypoplasia, constant nystagmus, strabismus, and photophobia." Wu et al. (2020) "identified six rhesus macaques with an albino appearance characterized by red hair and pink skin ... . These albino monkeys were 1-10 years old, and both male ... and female ... individuals were affected. Apparent horizontal nystagmus was observed in these monkeys ... . Compared with healthy individuals, the iris color was different in the albino subjects ... . ... Fundography of these albino subjects showed extensive hypopigmentation and the absence of a foveal centralis, while the choroid vasculature appeared to show the loss of pigmentation ... ." Peterson et al. (2023) report a less severe phenotype: “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.”

Associated gene: