Lethal Semi-Dominant: Merle

This double merle dog was born deaf and blind without recognizable eyes (anophthalmia). Other double merles can appear normal or so severely disabled as to not survive gestation.

We learned before that recessives are dangerous because when they are doubled up it often means that a vital bodily process is entirely broken leading to disease.  Recessive disease is more common than broken dominant disease because there’s no hiding from dominant alleles, they show up if you have one copy.  Thus, they are more likely to kill before reproduction and they are easier to weed out with selective breeding techniques.  It’s also easier to break an existing function than to have a mutation create a new product that is actively disruptive or lethal (entropy).

But as with most things in biology, all alleles don’t fall into an easy binary classification as dominant or recessive.  Another option is semi-dominant (also called incomplete dominant) where having one copy of a gene leads to a change in phenotype, but not as severe as the effect seen in a homozygous individual.  For example, long coat length in German Shepherds is a semi-dominant allele.  Two copies of the short coat gene leads to 2 inch hair, one copy of the long coat results in 3 inch hair, and two copies of the long coat allele result in 6 inch hair.

Some semi-dominant traits are harmful with a single copy and lethal (or profoundly debilitating) with a double dose.  In this respect they are worse than recessive disease because the single-copy state is actively selected for, creating a slew of carriers, and unlike recessives the single copy situation can still lead to defects.  Unfortunately, the lethality of these genes is often pre-natal so we don’t have to actively confront the disease and the morality of breeding for these traits. Out of sight, out of mind.

Three popular traits which we see in purebred dogs that are lethal semi-dominant are the merle gene, the bobtail gene, and the most prevalent hairless gene.

Double Merle, Single Merle, No Merle in the Aussie

Merle – Also known as “dapple” in Dachshunds and half of the equation (with the Harlequin gene that modifies the expression of the Merle gene; the Harlequin gene is also embryonic lethal in its homozygous form) in Harlequin Great Danes, the Merle gene is present in numerous dog breeds: Alaphaha Blue Blood Bulldogs, American Cocker Spaniels, American Pit Bull Terriers, American Staffordshire Terriers, Australian Shepherds, Beaucerons, Border Collies, Cardigan Welsh Corgis, Catahoula Leopard Dogs, Chihuahuas, Collies, Dachshunds, Great Danes, Koolies, Hungarian Mundis, Miniature Pinschers, Norwegian Hounds, Old English Sheepdogs, Pomeranians, Poodles, Pyrenean Shepherds, Shetland Sheepdogs, and is emerging in breeds like the Rat Terrier by way of down-low out-crosses.

The [semi-]dominant allele M acts on uniform pigmentation to produces an alternating pattern of dark versus light that is also known as dapple. The recessive allele produces uniform pigmentation when the dog is homozygous (mm). Heterozygous merle (mM) in an otherwise black dog produces a blue merle, and in an otherwise brown dog produces a red merle. Dogs homozygous for the dominant allele (MM) can be mildly affected to the naked eye or severely affected, depending on breed and even varying within a breed. Severely affected MM individuals are often nearly all white, deaf, sterile, and blind or affected by various visual abnormalities.

Because Merle has a varied penetrance, due to the fact that it disables color production to different degrees and only in some cells, the associated disease paths (mostly in the audio/visual area) are also variable, but much more prevalent in the homozygous state than with only one copy:

Reetz et al. reported hearing results for 38 dachshunds (Tekels in German): 11 double merles, 19 single merles, and 8 non-merles. They found hearing loss – slight to total, unilateral or bilateral – in 54.6% of double merles, in 36.8% of single merles, and in none of the non-merle.

In an unpublished study performed by myself and these investigators at Texas A&M University,7 70 merle dogs from five breeds (Shetland sheepdog, Australian shepherd, collie, Great Dane, and Catahoula leopard dog) had BAER hearing tests performed and merle genotype determined by DNA tests. Of 22 double merles, 8 were bilaterally deaf (36%) and 2 were unilaterally deaf (9%). Of 48 single merles only one was unilaterally deaf (2%), a Great Dane that also carried the piebald gene

It is believed that Merle leads to disease because the same mechanism that destroys or limits a cell’s ability to produce pigment that we interpret as coat color patterns also destroys a secondary function of those compounds which regulate blood supply in the tissue surrounding the sound sensing follicles within the ear.

The deafness, which usually develops in the first few weeks after birth while the ear canal is still closed, usually results from the degeneration of part of the blood supply to the cochlea (the stria vascularis). The nerve cells of the cochlea subsequently die and permanent deafness results. The…vascular degeneration…appears to be associated with the absence of pigment producing cells (melanocytes) in the blood vessels. All of the function of these cells are not known, but one role is to maintain high potassium concentrations in the fluid (endolymph) surrounding the hair cells of the cochlea; these pigment cells are critical for survival of the stria.

Iris Hypoplasia (2:00-5:00) in a homozygous Merle Aussie with a small Coloboma (1:00).

Homozygous merle (double dapple) is also associated with various disorders of the eye.  Iris hypoplasia (aniridia) is a disease where segments of the iris are missing or deficient; because the iris is unable to adjust the amount of light that enters the eye, this disorder causes photophobia which is the inability to see or extreme discomfort in bright light situations.  Similar and more severe is a coloboma where part of the iris, retina, and/or optic nerve is missing.

Another related condition is called Congenital Corectopia or ” eccentric pupils” where the pupil is not centered in one or both eyes.  In humans this is associated with chromosomal and central nervous system abnormalities.

At the extreme, the eye might be abnormally small and defunct (microophthalmia) or entirely missing (anophthalmia).

Since Merle is both common and desirable and appreciation for the gene’s deleterious nature is often trumped by denialism or ignorance, the double merle is one of the more compelling cases of aesthetics vs. health in dog breeding.

A blind and deaf double merle sheltie with very small eyes.

Some Shetland Sheepdog breeders in an attempt to create an all-merle line (if not a separate breed entirely) that always produced 100% merle puppies (to “breed true”) bred from several double merle sires that were apparently asymptomatic for merle related diseases.

A double merle parent is required to consistently produce an all-merle litter, preferably with a non-merle mate such that the entire litter would be the most desired homozyous merle.  But obviously such a breed is doomed to failure as the required breeding stock is the undesirable double merle x the undesirable non-merle.

Attempts to create a sustainable all-double-merle gene pool failed given that the asymptomatic quality of the initial double merle sires was not realized in the offspring and the highly bleached out coat was not as aesthetically pleasing to the fancy as the heterozygous merle.

The same is true of the Miniature Pinscher.  When Merle was banned from the breed standard in the German Kennel Club, some breeders refused to give up on the allele and tried to start their own all-merle breed.  It didn’t end well.

That’s a unique quality to lethal semi-dominants: you can never breed true.  This is why you’ll never see an all merle breed, a breed that has all natural bobtails, or an all hairless Xolo/Peruvian Inca Orchid/Chinese Crested.  For this to happen you need 100% saturation of the allele, dominant or recessive, and since the lethal semi-dominants are undesirable or never reach term, this state can never be reached (although some idiot breeders have tried).

In upcoming posts I’ll discuss two other prevalent lethal semi-dominant traits in dogs: bobtails and hairlessness.

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About Christopher

Christopher Landauer is a fifth generation Colorado native and second generation Border Collie enthusiast. Border Collies have been the Landauer family dogs since the 1960s and Christopher got his first one as a toddler. He began his own modest breeding program with the purchase of Dublin and Celeste in 2006 and currently shares his home with their children Mercury and Gemma as well. His interest in genetics began in AP Chemistry and AP Biology and was honed at Stanford University.