A missense mutation in the 20S proteasome beta 2 subunit of Great Danes having harlequin coat patterning

• Published in: Genomics (San Diego, Calif.) Calif.), 2011-04, Vol.97 (4), p.244-248
• Main Authors: Clark, Leigh Anne, Tsai, Kate L, Starr, Alison N, Nowend, Keri L, Murphy, Keith E
• Format: Article
• Language: English
• ISSN: 0888-7543
• DOI: 10.1016/j.ygeno.2011.01.003

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 25kb interval wherein all harlequin Great Danes are heterozygous for a common haplotype. This region contains one gene, PSMB7, which encodes the beta 2 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.