In other species: dog , domestic ferret , domestic cat , taurine cattle , sheep , American mink

Categories: Pigmentation phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609227 (trait) , 606526 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0012220: Griscelli syndrome type 3

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: no

Key variant known: yes

Year key variant first reported: 2013

Cross-species summary: FN acknowledges invaluable feedback from Cord Drögemüller that has led to the name of this phene being changed from "Coat colour, diluted" to "Coat colour, dilution, MLPH-related". At the same time, a new phene "Coat colour, dilution, generic" was created.

Molecular basis: By sequencing the MLPH gene in two dilute and one black rabbits, Lehner et al. (2013) discovered a "c.111-5C>A splice acceptor mutation within the polypyrimidine tract of intron 2", resulting in "p.QGL[37-39]QWA and a premature stop codon at p.K40*" as being a likely causal mutation for dilute. They also reported another likely causal mutation, namely a "frame shift mutation within exon 6 (c.585delG)" Adopting a comparative candidate gene strategy, Fontanesi et al. (2014) sequenced the rabbit MLPH gene and identified the same likely causal mutation mentioned by Lehner et al. (2013), namely "a deletion of one nucleotide in exon 5 (g.549853delG) that causes a shift in the reading frame that determines a completely different protein from the beginning of this exon . . . until the second half of exon 8 in which a stop codon would be introduced". By comparing the segregation of both variants with coat colour in 73 animals from two breeds, Demars et al. (2018) showed that only the deletion variant segregated perfectly with coat colour. Combining these results with other evidence, Demars et al. (2018) concluded that "The c.585delG variant remains as the most likely causative variant for coat color dilution in multiple rabbit breeds."

Breeds: Lionhead Dwarf, Loh, Netherland dwarf (Rabbit) (VBO_0001266).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: