To address coat color genetics in dogs, it pays to start from the beginning. Your dog’s body consists of trillions of cells. Most of these cells have a nucleus inside them, each of which contains 78 chromosomes. These chromosomes are made with deoxyribonucleic acid (DNA). DNA is then made up of nucleotides. In each cell, your dog will have about three billion base pairs of nucleotides. The unique pattern that these nucleotides form is what makes a gene special! So, while one gene might encode hair color into a hair shaft, another gene might be responsible for producing enzymes to digest food. For every gene, the code behind it is incredibly precise. One single mistake in the gene’s DNA sequence can have disastrous effects. In short, your dog’s DNA determines their coat color. Also, each hair follicle at the base of your pup’s hairs contains cellular material that’s rich in DNA. Along with this, melanocytes surround each hair follicle. There are two types of melanin that melanocytes are responsible for: eumelanin (brown-black), and phaeomelanin (red-yellow). Depending on the underlying genetic influence, a melanocyte produces either type of melanin.
ALLELES AND LOCI:
In genetics, a locus is a fixed position on a chromosome where a specific gene resides. Each gene resides at a locus on a chromosome in two copies, one copy for each gene inherited from each parent. These copies, however, aren’t necessarily identical. When the copies of a gene are different from one another, they’re known as alleles. To understand dog coat color genetics, it’s important to get to know each locus, first.
A (AGOUTI) LOCUS:
The A-locus is governed by the agouti signaling protein (ASIP) gene. This gene interacts with another gene known as MC1R to control red and black pigment switching in dogs. The ASIP gene governs four different alleles. These are ay = Fawn/sable, aw = Wild sable, t = Black-and-tan, and a = Recessive black. These four alleles work in a hierarchy and ay is the most dominant of them all.
E (EXTENSION) LOCUS:
The E locus is governed by the MC1R gene. It has three possible forms: black (E), melanistic mask (Em), and yellow/red (ee). The “E” allele allows a dog to produce eumelanin or black pigment. If a dog carries two copies of the E allele (E/E), it can produce black pigment. However, a mutation of the MC1R gene can cause a dog’s cells to only produce phaeomelanin in place of eumelanin. This mutation is represented as the “e” allele.
If a dog carries one copy of “E” and one copy of “e”, they can produce black pigment. The “E/e” dog passes on E to half of its offspring, and e to the other half, the latter of which can produce a yellow/red coat if inherited with another copy of e from the other parent. Because the “e” allele is recessive, a dog must have two copies of it to express the yellow or red coat color. A dog with e/e expression will have a coat that is white, cream, yellow, apricot, or red in color.
K (DOMINANT BLACK) LOCUS:
The K locus consists of three alleles. The first K locus allele is KB, or dominant black. This allele reduces or eliminates the expression of the A locus. This mutation is dominant, so your dog only needs one copy of KB to affect the expression of the A locus. A KB/KB or KB/n dog is solid black in color. The next allele is the “brindling” allele, written as “Kbr“. The Kbr allele allows the A locus to come through but causes brindling of the agouti patterns. However, this allele is recessive to the dominant black allele. So, if your dog’s genotype is KB/Kbr, they will only be solid black and not brindle. The last allele is ky, or recessive non-black. This allele allows the agouti gene to come through without any brindling. So, a dog with two copies of ky will show whatever it has on the A locus, but will still have black nose pigment and may have some black markings, too. In contrast, a dog with both KB and ky will not be able to show any colors from the A locus.
B (BROWN) LOCUS:
The B locus is the home of the liver coat color. This gene affects eumelanin (black pigment). If a dog has a liver coat, their nose is typically brown or pink, and the eyes amber or light brown. The liver gene itself is recessive, so “b” represents liver, and “B” is non-liver, or black. A genotype of B/B or B/b would create a black dog. So, in order for a dog to have a liver coat, it must have the genotype b/b. If your dog has this genotype, it’s genetically impossible for them to have black or gray hair in their coat. The D locus commonly influences the B locus, leading to dilute versions of the liver coat.
D (DILUTE) LOCUS:
The D locus is responsible for lightening the coat. This gene is recessive, so “d” represents dilute, and “D” represents non-dilute. In order for your dog to have a dilute coat, it must have the “d/d” genotype. A dog that is “D/d” or “DD” will have a normal coat. The dilution gene mostly affects eumelanin (black and liver pigment), but phaeomelanin (red) can lighten, too. So, when a dog has “d/d” alleles, a black dog becomes blue or slate. A liver dog becomes isabella or lilac. The eyes will also lighten to amber, which is typically paler than the amber eyes seen in liver dogs.
M (MERLE) LOCUS:
The merle gene is responsible for diluting random sections of the coat to a lighter color, especially in black, liver, blue, or isabella dogs. There is a large number of different merle alleles that affect the coat in different ways. In the merle gene, there is an extra portion of DNA in the dog’s genome. This is its SINE insertion. The longer the insertion, the greater the effect on the dog’s coat.
So, for example, the harlequin merle gene (Mh) has a length of 269-280. In contrast, the standard merle gene (M) is 265-268, the atypical merle is 247-254, and the cryptic merle is 200-230. So, while the cryptic merle insertion isn’t long enough to affect the coat, harlequin merle dilutes gray areas to white or light gray. Because this is the longest insertion, the risk of serious eye and ear defects is highest with this form of merle. It is not safe to breed two merle dogs together for this reason.
H (HARLEQUIN) LOCUS:
The harlequin gene occurs on the H Locus of the Great Dane. This gene is a modifier. This means that, when inherited alongside another gene, it affects the way that the gene appears. If a dog inherits the modifier but not the gene that it modifies, there is no obvious change to the gene. So, when a Great Dane inherits both the harlequin gene and the merle gene, the areas between their dark patches become pure white. Sometimes, gray ticking or patches will develop, too. This means that a blue (black) merle becomes white with black patches, as the gray in its coat turns to white.
The modifier also affects phaeomelanin (red), so even if a dog is sable, their coat will become “fawnequin” with tan and black patches on a white base. Unfortunately, the harlequin gene may be a dominant embryonic lethal gene. This means that all “H/H” puppies die before birth, leaving only “H/h” puppies to be born.
S (SPOTTING) LOCUS:
Most white spots on dogs are the result of genes on the S locus. White spotting can occur with any coat color and will take over both eumelanin (brown/black) and phaeomelanin (yellow/red). The white spotting gene stops the cells from producing skin pigment, causing white areas in the coat. So far, only two alleles are known to exist on the S locus. These are S, which produces no or very little white, and sp, which produces piebald patterns. A third allele might exist on the S locus, but it has not yet been proven. This allele is “extreme white” sw.
BLACK HAIR FOLLICULAR DYSPLASIA, BHFD:
Black hair follicular dysplasia (BHFD) is inherited as an autosomal recessive trait and is a type of alopecia (hair loss) that only affects areas of black fur. It is seen in bicolour and tricolour dogs. Pups are born normally, but may show a dulling of the normal dark, glossy black hair. The hair on adjacent white skin grows normally. With time black hairs become brittle and break easily. Black hair fails to grow, and skin can become scaly. It is thought that BHFD may be related to the condition “colour dilution alopecia”, in which hair loss is seen in colour dilute animals (e.g. blue and fawn dogs). Both conditions seem to involve defects in the processing and transport of the skin and hair pigment melanin. With BHFD, the hair follicles in areas of black hair are abnormal, with clumps of melanin, distorted follicles and hyperkeratosis seen on histopathology. These abnormal hair follicles are prone to infection, and so affected areas of skin can develop bacterial folliculitis, an infection that is very irritating and can sometimes lead to deeper skin infection (pyoderma). Treatment is symptomatic only, and abnormal or missing hairs will not be replaced by normal hairs. Topical antiseptics or antibiotics are used for bacterial folliculitis. Antiseborrhoeic shampoos and oil rinses are often helpful, and general skin treatments such as omega fatty acids are often given. Other treatments recently reported of possible benefit include melatonin, etretinate (a synthetic aromatic retinoid) and niacinamide.
COAT COLOUR DILUTION ALOPECIA, CDA:
Color dilution alopecia or CDA is an inherited type of hair loss that affects dogs that have a dilute fur color. Blue (silvery or bluish-gray) and fawn (soft brown) are the two most common dilute fur colors in dogs. Many different breeds can sport these fur colors. Also known as color mutant alopecia or blue Doberman syndrome, this inherited disease is a result of a recessive gene that causes hair shafts to break off at the base, along with overall stunted hair growth. CDA is not fully understood, but it is thought that hair follicle damage occurs in dogs with this condition due to melanin clumping in the hair shafts. Typically, puppies carrying the inherited trait have normal coats for their first few months but begin to lose patches of hair as they enter late puppy hood or early adulthood. Although CDA does not cause skin inflammation or irritation directly, occasionally, bits of broken hair and skin cells can block the hair follicles, leading to secondary bacterial infections that cause itchy or flaky skin. Typically, however, dogs with this condition have normal skin.
EUMELANIN AND PHEOMELANIN:
There are two types of pigment that influence the color of your pup’s coat. These pigments are eumelanin and phaeomelanin. Most dogs’ coats contain both eumelanin and phaeomelanin. In these cases, the A locus determines how the two pigments mix in the coat. But what exactly are these pigments?
Eumelanin is responsible for black pigment. However, other genes can turn eumelanin into other colors. These colors include liver (brown), blue (gray), and isabella. If a dog has a gene that turns its eumelanin into another color, the entire coat color changes. This is because the gene changes the production of the eumelanin, meaning that none of the dog’s cells can produce the original pigment.
Phaeomelanin is responsible for red pigment. However, the name “red” applies to every pigment from deep red to cream, encompassing colors like yellow and orange, too. Unlike eumelanin, phaeomelanin does not occur in the nose or eyes. So, any gene affecting the phaeomelanin in the coat will not affect the eyes or nose.
CYSTINURIA (MINIATURE PINSCHER TYPE), CYST:
Cystinuria (miniature pinscher type) is an inherited disease affecting kidney function in dogs. The SLC7A9 gene codes for a protein that allows the kidneys to transport cysteine and other amino acids from the urine. Normal kidneys reabsorb the Amino Acid cystine so that only small amounts pass into the urine, while dogs with mutations of both copies of the SLC7A9 gene fail to reabsorb cystine allowing high amounts to pass into the urine, hence the name cystinuria. Cystine can form crystals and/or stones in the urinary tract which can block the ureters or Urethra and stop the normal flow of urine. Affected male dogs present with symptoms related to cysteine bladder stones around one year of age, however female dogs tend to develop symptoms later than males. Symptoms of disease include straining to urinate, frequent urination of small volumes or inability to urinate. In miniature pinschers, males and females are equally affected with excess cysteine in the urine, but obstruction of urine flow is more common in males due to differences in anatomy. Dogs with cystinuria often have recurrent inflammation of the urinary tract and if not treated, urinary stones can cause urinary tract infections, kidney failure and even death.
DEGENERATIVE MYELOPATHY, DM:
Degenerative myelopathy caused by Mutation of the SOD1 gene is an inherited neurologic disorder of dogs. This mutation is found in many breeds of dog, though it is not clear whether all dogs carrying two copies of the mutation will develop the disease. The variable presentation between breeds suggests that there are environmental or other genetic factors responsible for modifying disease expression. The average age of onset for dogs with degenerative myelopathy is approximately nine years of age. The disease affects the White Matter tissue of the spinal cord and is considered the canine equivalent to amyotrophic lateral sclerosis (Lou Gehrig’s disease) found in humans. Affected dogs usually present in adulthood with gradual muscle Atrophy and loss of coordination typically beginning in the hind limbs due to degeneration of the nerves. The condition is not typically painful for the dog, but will progress until the dog is no longer able to walk. The gait of dogs affected with degenerative myelopathy can be difficult to distinguish from the gait of dogs with hip dysplasia, arthritis of other joints of the hind limbs, or intervertebral disc disease. Late in the progression of disease, dogs may lose fecal and urinary continence and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of symptoms. Affected medium to large breed dogs can be difficult to manage and owners often elect euthanasia when their dog can no longer support weight in the hind limbs. Affected small breed dogs often progress more slowly than affected large breed dogs and owners may postpone euthanasia until the dog is paraplegic.
Hyperuricosuria is an inherited condition that causes an excessive uric acid level in a dog’s urine. High levels of uric acid in dogs can cause the formation of painful kidney or bladder stones (called urate stones).
This condition can be life-threatening in male dogs if their urinary tract gets blocked by urate stones.
MUCOPOLYSACCHARIDOSIS VI (POODLE TYPE)*, MVI:
Lysosomal storage diseases are rare inherited metabolic disorders that result in cellular dysfunction. One type of lysosomal storage disease, mucopolysaccharidosis type VI (MPS VI), is caused by a deficiency of the arylsulfatase B (ARSB) enzyme. This enzyme is responsible for breaking down large sugar molecules known as glycosaminoglycans in the recycling centers (lysosomes) of cells. Insufficient ARSB activity causes glycosaminoglycans to build up within the cells, preventing normal function and eventually causing cell death. MPS VI has been identified in humans, dogs, cats, and rodents. Clinical signs in dogs include retarded growth, progressive corneal cloudiness, and skeletal deformities. Affected dogs require intensive nursing care and are often euthanized at a young age due to progressive disease.
PRIMARY LENS LUXATION, PLL:
The lens of the eye normally lies immediately behind the iris and the pupil, and is suspended in place by a series of fibers, called zonular ligaments. It functions to focus light rays on the retina, in the back of the eye. When partial or complete breakdown of the zonular ligaments occurs, the lens may become partially dislocated (Lens Subluxation) or fully dislocated (Lens Luxation) from the lens’ normal position. Primary Lens Luxation is a heritable disease in many breeds, including many terrier breeds (Jack Russell, Bedlington, Fox, Manchester, Miniature Bull, Scottish, Sealyham, Welsh, West Highland White), Tibetan Terrier, Border Collie, Brittany Spaniel, German Shepherd and Welsh Corgi. In these breeds, spontaneous luxation of the lens occurs in early adulthood (most commonly 3-6 years of age) and often affects both eyes, although not necessarily at the same time. Primary Lens Luxation is caused by an inherent weakness in the zonular ligaments which suspends the lens. Lens Luxation can also occur secondary to other primary problems of the eye, including inflammation, cataracts, glaucoma, cancer, and trauma. Lens Luxation can lead to inflammation (Uveitis) and Glaucoma (increased intraocular pressure). This can result in painful, teary, red eyes that may look hazy or cloudy. Both Uveitis and Glaucoma are painful and potentially blinding diseases if not identified and treated early.
GLOSSARY OF GENETIC TERMS:
NEGATIVE / CLEAR [NO VARIANT DETECTED]
No presence of the variant (mutation) has been detected. The animal is clear of the disease and will not pass on any disease-causing mutation.
CARRIER [ONE COPY OF THE VARIANT DETECTED]
This is also referred to as HETEROZYGOUS. One copy of the normal gene and copy of the affected (mutant) gene has been detected. The animal will not exhibit disease symptoms or develop the disease. Consideration needs to be taken if breeding this animal - if breeding with another carrier or affected or unknown then it may produce an affected offspring.
POSITIVE / AT RISK [TWO COPIES OF THE VARIANT DETECTED]
Two copies of the disease gene variant (mutation) have been detected also referred to as HOMOZYGOUS forthe variant. The animal may show symptoms (affected) associated with the disease. Appropriate treatment should be pursued by consulting a Veterinarian.
POSITIVE HETEROZYGOUS [ONE COPY OF THE DOMINANT VARIANT DETECTED]
Also referred to as POSITIVE ONE COPY or POSITIVE HETEROZYGOUS. This result is associated with a disease that has a dominant mode of inheritance. One copy of the normal gene (wild type) and affected (mutant) gene is present. Appropriate treatment should be pursued by consulting a Veterinarian. This result can still be used to produce a clear offspring.
NORMAL BY PARENTAGE HISTORY
The sample submitted has had its parentage verified by DNA. By interrogating the DNA profiles of the Dam, Sire and Offspring this information together with the history of the parents excludes this animal from having the disease. The controls run confirm that the dog is NORMAL for the disease requested.
NORMAL BY PEDIGREE
The sample submitted has had its parentage verified by Pedigree. The pedigree has been provided and details(genetic testing reports) of the parents have been included. Parentage could not be determined via DNA profile as no sample was submitted.
NO RESULTS AVAILABLE
Insufficient information has been provided to provide a result for this test. Sore and Dam information and/or sample may be required. This result is mostly associated with tests that have a patent/license and therefore certain restrictions apply.
The sample submitted has failed to give a conclusive result. This result is mainly due to the sample failing to “cluster” or result in the current grouping. A recollection is required at no charge. DNA PROFILE Also known as a DNA fingerprint. This is unique for the animal. No animal shares the same DNA profile. An individual’s DNA profile is inherited from both parents and can be used for verifying parentage (pedigrees). This profile contains no disease or trait information and is simply a unique DNA signature for that animal.
PARENTAGE VERIFICATION/ QUALIFIES/CONFIRMED OR DOES NOT QUALIFY/EXCLUDED
Parentage is determined by examining the markers on the DNA profile. A result is generated and stated for all DNA parentage requests.Parentage confirmation reports can only be generated if a DNA profile has been carried out for Dam, Offspring, and possible Sire(s).
A feature that an animal is born with (a genetically determined characteristic).Traits are a visual phenotype that range from colour to hair length, and also includes certain features such as tail length. If an individual is AFFECTED for a trait then it will show that characteristic eg.AFFECTED for the B (Brown) Locus or bb will be brown/chocolate.
POSITIVE – SHOWING THE PHENOTYPE
The animal is showing the trait or phenotype tested.