In other species: Chinese giant salamander

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 113750 (trait) , 609802 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2017

Species-specific name: Tiger-eye or Goat-eye

Species-specific description: Mack et al. (2017): "A unique eye color, called tiger-eye, segregates in the Puerto Rican Paso Fino (PRPF) horse breed and is characterized by a bright yellow, amber, or orange iris."

Inheritance: Mack et al. (2017): "Pedigree analysis identified a simple autosomal recessive mode of inheritance for this trait" (i.e., tiger eye0

Mapping: Mack et al. (2017): "A genome-wide association study (GWAS) with 24 individuals identified a locus on ECA 1 reaching genome-wide significance (Pcorrected = 1.32 × 10-5). This ECA1 locus harbors the candidate gene, Solute Carrier Family 24 (Sodium/Potassium/Calcium Exchanger), Member 5 (SLC24A5), with known roles in pigmentation in humans, mice, and zebrafish. Humans with compound heterozygous mutations in SLC24A5 have oculocutaneous albinism (OCA) type 6 (OCA6) [see MIM hyperlink 113750 above], which is characterized by dilute skin, hair, and eye pigmentation, as well as ocular anomalies."

Markers: Kreuzer et al. (2010) identified six variants within the equine SLC24A5 gene. One of these variants, "an intronic mutation, which is localized 23 bp upstream of exon 5" which they called SME5 (g.13858G>T; ENSECAG00000018641, 12.12.09) was associated with "fading black" in a sample of "31 black horses and 23 fading black horses" from a range of unspecified breeds. {12 Dec 2019: FN thanks Corinne Benavides-Gyger for alerting him to this publication}

Molecular basis: Mack et al. (2017): "Twenty tiger-eye horses were homozygous for a nonsynonymous mutation in exon 2 (p.Phe91Tyr) of SLC24A5 (called here Tiger-eye 1), which is predicted to be deleterious to protein function. Additionally, eight of the remaining 12 tiger-eye horses heterozygous for the p.Phe91Tyr variant were also heterozygous for a 628 bp deletion encompassing all of exon 7 of SLC24A5 (c.875-340_1081+82del), which we will call here the Tiger-eye 2 allele. None of the 122 brown-eyed horses were homozygous for either tiger-eye-associated allele or were compound heterozygotes. Further, neither variant was detected in 196 horses from four related breeds not known to have the tiger-eye phenotype."

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

Breed: Paso Fino (Horse) (VBO_0001040).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene: