In other species: domestic cat , water buffalo , franciscana , sika deer

Categories: Pigmentation phene

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 600201 (gene) , 606202 (gene) , 184745 (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: 2013

Species-specific description: As noted by Xu et al. (2013), "The white tiger is not a true albino, in that although pheomelanin is largely absent, eumelanin is present in the eyes and in the hairs of stripes".

History: As reported by Xu et al. (2013) white Bengal tigers "were once observed sporadically in the wild on the Indian subcontinent, with the oldest record dating back to the 1500s [Jackson, 1988]. In 1951, a male white tiger named Mohan was captured in Rewa, now part of Madhya Pradesh in India, from which numerous white tigers were bred for captivity [ Robinson, 1969; Robinson, 1976; Thornton, 1978; Thornton et al., 1967; Maruska, 1987]."

Inheritance: Autosomal recessive inheritance was documented by Thornton et al. (1967).

Mapping: Having shown no association between the white phenotype of Bengal tigers and polymorphisms in any of the obvious candidate coat-colour genes, Xu et al. (2013) undertook a herculean effort that is very much a sign of the times, namely whole-genome sequencing three Bengal tigers (which are parents in a captive-bred family), and, from the sequence data, identifying 509,220 SNPs, each of which was aligned to the tiger reference genome. They then performed a GWAS on 7 white and 9 wild-type tigers (from the same captive-bred family), each genotyped with the identified SNPs, yielding 172,554 informative SNPs. The GWAS mapped the white locus to two adjacent scaffolds (75 and 1458). Linkage mapping within these two scaffolds highlighted a 3.3Mb candidate region, which (according to the tiger reference genome) contains 23 genes.

Molecular basis: Careful examination of the whole-genomes sequence data from the three parents of the captive-bred family segregating for the white phenotype, combined with "restriction-site-associated DNA sequencing (RAD-seq)" of the 13 offspring in the same family, enabled Xu et al. (2013) to identify a candidate mutation in each of two genes in the candidate region (see Mapping section). Genotyping of other Bengal tigers (20 white and 110 wild-type) for both mutations revealed the causal mutation to be a missense mutation, namely a "C-to-T transition in exon 7 in SLC45A2 (solute carrier family 45 member 2, also known as MATP or AIM-1), which corresponds to alanine-to-valine substitution at amino acid residue 477 (A477V)".

Associated gene: