In other species: dog , domestic cat , horse , cattle , rabbit

Possibly relevant human trait(s) and/or gene(s) (MIM number): 609227

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: Also known as Coat colour, dilution

Species-specific name: Silver-blue coat colour

Species-specific symbol: p

Inheritance: The silver-blue coat colour, which is analogous to the dilute phenotype in other species, is inherited as an autosomal recessive at the Silver locus (Anistoroaei and Christensen, 2007). The symbol for the recessive allele is p.

Mapping: Anistoroaei and Christensen (2007) linkage-mapped this locus to chromosome NVI13, and showed that this locus was coincident with "A Canis familiaris BAC clone containing the melanophilin gene (which generates 'silver-like' phenotype in dog)", strongly suggesting that the silver locus in American mink is the MLPH locus. Using three microsatellites from a contig containing MLPH, Cicera et al. (2013) confirmed these results by linkage-mapping all three markers to the appropriate region of chromosome NVI3. They also reported physically mapping one of the microsatellites to NVI3q1.3-2.2.

Molecular basis: By sequencing the positional candidate MLPH gene (see mapping section above) in silverblue, violet and wild-type mink, Cirera et al. (2013) "identified two deletions of the entire intron 7 and of the 5′ end of intron 8 in the sequence of the Silverblue MLPH gene". Investigation of MLPH mRNA revealed that "the Silverblue animals completely lack exon 8, which encodes 65 residues, of which 47 define the Myosin Va (MYO5A) binding domain. This may cause the incorrect anchoring of the MLPH protein to MYO5A in Silverblue animals, resulting in an improper pigmentation as seen in diluted phenotypes." Interestingly, even though the silverblue allele lacks the entire exon 8, it has "retained part of the intron 8 in the coding region. This introduces a stop codon, leading to a truncated protein 284 residues long that is lacking almost all MYO5A Va and all actin-binding domains". In addition, the authors reported that "in the MLPH mRNA of wt, Violet and Silverblue phenotypes, part of intron 8 is retained resulting in a truncated MLPH protein, which is 359 residues long in wt and Violet and 284 residues long in Silverblue."

Associated gene: