In other species: horse

Possibly relevant human trait(s) and/or gene(s) (MIM number): 617745

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2019

Cross-species summary: pheomelanin dilution, pigment intensity

Species-specific name: This entry describes the Intensity (I) locus; sometimes called the Intense (Int) locus

Species-specific symbol: I; previously called Int

Species-specific description: Hédan et al. (2019): "Thanks to a multiple step GWAS approach, we confirmed that solid white coat color in dogs may result from the absence of eumelanin (e/e at the MC1R locus) and an extreme dilution of phaeomelanin, confirming the hypothesis of Sponenberg and Rothschild [2001] on the existence of an I locus and later, the work of Schmutz and Berryere [2007; J. Heredity]."

History: As summarised by Carver (1984), Iljin (1932) proposed a locus with "a series of phaeomelanin intensifying alleles" with order of dominance "Int/- (cream) > int^f/- (fawn) > int/int (tan)". Iljin (1941) named the locus "intensification of the zonarity", with the symbol "Int", where "zonarity" refers to the differentially-pigmented band on a hair fibre that is characteristic of the agouti coat colour (OMIA 000201-9615). Following Iljin (1941), Carver (1984) called this the Int locus. Citing Iljin (1932) and Carver (1984), Sponenberg and Rothschild (2001) hypothesised "an autosomal locus [that] affects the intensity of phaeomelanic areas but leaves eumelanic areas relatively unchanged". They called this the Intense locus (Int). Schmutz and Berryere (2007; Animal Genetics) changed the locus symbol to "I", to render it consistent with the convention for single-letter canine pigmentation locus symbols. Hédan et al. (2019) refer to the locus as "Intensity" with symbol "I", which can now be regarded as the preferred name and symbol. (Thanks to Sheila Schmutz for invaluable contributions to this summary)

Mapping: Hédan et al. (2019) mapped the I locus to chromosome CFA20 at around 55Mb.

Molecular basis: Hédan et al. (2019) "identified a unique missense variant that was located in the first exon of MFSD12 [CFA20: g.55,850,145C>T]. . . , based on alignments with the human genome and the annotation of the human orthologous transcript ENST00000355415: MFSD12: p.(Arg51Cys). This dog variant is exactly orthologous to the human variant rs751585493 (ENST00000355415 Chr19:3557253 G > A; p.(Arg51Cys)."

Associated gene: