What is the PSMB7 mutation in Great Danes?

The PSMB7 mutation in Great Danes is a missense mutation located in the 20S proteasome beta 2 subunit on chromosome 9.

This specific genetic variant has been identified by researchers as the cause of the Harlequin trait. The mutation is dominant, and when a dog inherits one copy of it (the H allele) alongside the Merle gene (M), the Harlequin modifier removes the dilute background pigment caused by the Merle gene, increasing the size of the fully pigmented regions and leaving pure white areas.

However, researchers do not yet fully understand the exact mechanism by which the PSMB7 mutation interacts with the SILV gene (which causes the merle pattern) to produce this loss of background pigment.

Additionally, the PSMB7 mutation is considered embryonic-lethal. When an embryo inherits two copies of this mutation (a homozygous HH genotype), it results in embryonic death very early in the pregnancy. Consequently, all living Harlequin Great Danes possess only one copy of the PSMB7 mutation (heterozygous Hh).