A missense mutation in the 20S proteasome β2 subunit of Great Danes having harlequin coat patterning.
Harlequin is a pigmentary trait of the domestic dog that is controlled by two autosomal loci: the melanosomal gene, SILV, and a modifier gene, harlequin (H), previously localized to chromosome 9. Heterozygosity for a retrotransposon insertion in SILV and a mutation in H causes a pattern of black patches on a white background. Homozygosity for H is embryonic lethal. Fine mapping of the harlequin locus revealed a 25 kb interval wherein all harlequin Great Danes are heterozygous for a common haplotype. This region contains one gene, PSMB7, which encodes the β2 catalytic subunit of the proteasome. Sequence analysis identified a coding variant in exon 2 that segregates with harlequin patterning. The substitution predicts the replacement of a highly conserved valine with a glycine. Described herein is the identification of a naturally-occurring mutation of the ubiquitin proteasome system that is associated with a discernable phenotype of dogs.
Department of Genetics and Biochemistry, College of Agriculture, Forestry, and Life Sciences, Clemson University, Clemson, SC 29634-0318, USA. lclark4@clemson.edu
Leigh Anne
LA
Clark
Kate L
KL
Tsai
Alison N
AN
Starr
Keri L
KL
Nowend
Keith E
KE
Murphy
D000595:Amino Acid Sequence; D000818:Animals; D001947:Breeding; D002874:Chromosome Mapping; D004285:Dogs / Q000033:anatomy & histology* / Q000235:genetics*; D006200:Hair Color / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D018626:Retroelements / Q000235:genetics; D017422:Sequence Analysis, DNA; D058951:gp100 Melanoma Antigen / Q000235:genetics
D018626:Retroelements; D058951:gp100 Melanoma Antigen; D046988:Proteasome Endopeptidase Complex