title: Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle.
abstract: In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large-scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild-type allele at the co-dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named 'cool gray'. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed.
authors.affiliation: GIGA-R and Faculty of Veterinary Medicine, University of Liège, 1 avenue de l'hôpital, 4000 Liège, Belgium.
authors.forename: Wanbo
authors.initials: W
authors.lastname: Li
authors.affiliation: Bovine Clinic, FARAH and Faculty of Veterinary Medicine, University of Liège, 20 boulevard de Colonster 4000 Liège, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Sartelet
authors.affiliation: GIGA-R and Faculty of Veterinary Medicine, University of Liège, 1 avenue de l'hôpital, 4000 Liège, Belgium.
authors.forename: Nico
authors.initials: N
authors.lastname: Tamma
authors.affiliation: GIGA-R and Faculty of Veterinary Medicine, University of Liège, 1 avenue de l'hôpital, 4000 Liège, Belgium.|GIGA-Genomics platform, University of Liège, 1 avenue de l'hôpital, 4000 Liège, Belgium.
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
authors.affiliation: GIGA-R and Faculty of Veterinary Medicine, University of Liège, 1 avenue de l'hôpital, 4000 Liège, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.affiliation: GIGA-R and Faculty of Veterinary Medicine, University of Liège, 1 avenue de l'hôpital, 4000 Liège, Belgium.
authors.forename: Carole
authors.initials: C
authors.lastname: Charlier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D002417:Cattle / Q000235:genetics*; D016368:Frameshift Mutation; D005838:Genotype; D006200:Hair Color / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D010858:Pigmentation / Q000235:genetics; D059386:Reverse Genetics; D017384:Sequence Deletion
chemical_list: D048868:Adaptor Proteins, Signal Transducing
keywords: KITLG; MLPH; OMIA 00206-9913; bovine; cool gray; disruptive mutation; whole-genome/whole-exome sequence