A frameshift mutation in the melanophilin gene causes the dilute coat colour in rabbit (Oryctolagus cuniculus) breeds

Abstract

In rabbit, the dilute locus is determined by a recessive mutated allele (d) that causes the dilution of both eumelanic and pheomelanic pigmentations. In mice, similar phenotypes are determined by mutations in the myosin VA, Rab27a and melanophilin (MLPH) genes. In this study, we investigated the rabbit MLPH gene and showed that a mutation in this gene appears responsible for the dilute coat colour in this species. Checkered Giant F1 families segregating for black and grey (diluted or blue) coat colour were first genotyped for a complex indel in intron 1 of the MLPH gene that was completely associated with the coat colour phenotype (θ = 0.00; LOD = 4.82). Then, we sequenced 6357 bp of the MLPH gene in 18 rabbits of different coat colours, including blue animals. A total of 165 polymorphisms were identified: 137 were in non-coding regions and 28 were in coding exons. One of them was a frameshift deletion in exon 5. Genotyping the half-sib families confirmed the complete cosegregation of this mutation with the blue coat colour. The mutation was analysed in 198 rabbits of 23 breeds. All Blue Vienna and all other blue/grey/ash rabbits in other breeds (Californian, Castor Rex, Checkered Giant, English Spot, Fairy Marburg and Fairy Pearly) were homozygous for this deletion. The identification of MLPH as the responsible gene for the dilute locus in rabbit provides a natural animal model for human Griscelli syndrome type 3 and a new mutant to study the role of this gene on pigmentation.

Interactions of allele E of the MC1R gene with FM and mutations in the MLPH gene cause the five-gray phenotype in the Anyi tile-like gray chicken

“…Studies have shown that the protein complexes encoded by MLPH, RAB27A, and MYO5A are required for melanosome transport (Ménasché et al, 2003). In several species, such as humans, cats, dogs, horse, mink, rabbit, and quail, defects in MYO5A, RAB27A, and MLPH were found to cause a phenotypically identical pigmentary dilution (Wilson et al, 2000;Matesic et al, 2001;Ménasché et al, 2000Ménasché et al, , 2003Philipp et al, 2005;Ishida et al, 2006;Bed'hom et al, 2012;Cirera et al, 2013;Fontanesi et al, 2014). Results of the association analysis showed that only one SNP in MLPH was significantly associated with the gray plumage color phenotype, suggesting that the MLPH gene might be closely associated with the gray plumage color phenotype.…”

“…Studies in chicken and quail showed that the lavender plumage color dilution phenotype was caused by a mutation in the MLPH gene (Vaez et al, 2008;Bed'hom et al, 2012), and that the protein complexes encoded by MLPH, RAB27A, and MYO5A were required for melanosome transport. In fact, mutations in MLPH, RAB27A, and MYO5A can all lead to the dilution phenotype in animals (Matesic et al, 2001;Ménasché et al, 2003;Philipp et al, 2005;Ishida et al, 2006;Bed'hom et al, 2012;Cirera et al, 2013;Fontanesi et al, 2014). Presumably, the "gray" phenotype is derived from the black phenotype (i.e., black feathers, shanks, skin, beak, and comb).…”

High‐throughput SNP discovery in the rabbit (Oryctolagus cuniculus) genome by next‐generation semiconductor‐based sequencing

“…, , ; Fontanesi et al . , , ) and (iii) a first copy number variation genomic map has been obtained using array comparative genome hybridization in a few rabbits (Fontanesi et al . ).…”

A premature stop codon in theTYRP1gene is associated with brown coat colour in the European rabbit (Oryctolagus cuniculus)

“…Obtained PCR products were sequenced using the Big Dye v3.1 cycle sequencing kit (Applied Biosystems) as previously described (Fontanesi et al . ). Sequencing reactions were loaded on an ABI3100 Avant sequencer (Applied Biosystems).…”

“…), a deletion in the melanophilin ( MLPH ) gene causes the dilute coat colour phenotype (Fontanesi et al . ), and mutations in the tyrosinase ( TYR ) genes determine alleles of the albino ( C ) locus (Aigner et al . ).…”