What causes embryonic death in Harlequin Great Danes?

Embryonic death in Harlequin Great Danes is caused by inheriting two copies of the Harlequin gene, resulting in a homozygous (HH) genotype.

The Harlequin gene acts as an embryonic lethal gene when inherited in this double form. When an embryo possesses the HH genotype, it fails to develop properly and is reabsorbed into the womb very early in pregnancy.

Because this early embryonic failure does not result in observable stillbirths, no living dog has ever been observed or tested with two copies of the Harlequin mutation. Consequently, every dog displaying or carrying the Harlequin pattern has only a single copy of the gene, making them heterozygous (Hh). This lethal homozygous effect is also the reason why Harlequin Great Danes are not “true breeding” and will almost always produce merle offspring rather than exclusively Harlequin litters