What is the lethal effect of the Harlequin gene?

The Harlequin gene is embryonic-lethal when a dog inherits two copies of it. If a puppy inherits this homozygous HH genotype, the mutation causes embryonic death very early during pregnancy, meaning the embryo fails to form entirely and is instead reabsorbed into the womb.

Because this early embryonic failure does not result in observable stillbirths, a dog with two copies of the Harlequin gene has never been observed or tested. Consequently, every living dog that displays or carries the Harlequin trait only possesses a single copy of the mutation, making them heterozygous (Hh). This lethal homozygous effect is the reason why Harlequin Great Danes are not “true breeding,” meaning they cannot consistently produce exclusively Harlequin litters and will almost always produce merle offspring as well.