REGENCY'S MAUI KOA Genetic Vet Report by embarkvet.com Test Date: October 20, 2018 MULTIDRUG SENSITIVITY CHROMOSOME 14

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1 Owner Name: Regency Ranch Dog Name: Regency's Maui Koa Sex: Male (intact) Breed type: Purebred Breed: Golden Retriever Microchip #: **** REGENCY'S MAUI KOA Genetic Vet Report by embarkvet.com Test Date: October 20, AT RISK Summary 2 CARRIER Not At Risk Good news! Regency's Maui Koa did not test positive for any of the genetic diseases that Embark screens for. Carrier/ Not Affected Maui Koa is a carrier for 2 of the genetic diseases that Embark tests for. Maui Koa has inherited a recessive allele for a genetic trait or mutation. This is not enough to cause symptoms of the disease, but is important to bear in mind if Maui Koa is bred, that he is not bred to another carrier or a dog that is affected. GOLDEN RETRIEVER COMMON CONDITIONS MULTIDRUG SENSITIVITY CHROMOSOME 14 Regency's Golden American Reveille has two healthy alleles at MDR1 and would be expected to exhibit normal drug reactions. Please note that a percentage of dogs without the MDR1 mutation still exhibit side effects to some medications; for flea, tick, and heartworm preventatives, the most common side effects are lethargy and nausea. If Regency's Golden American Reveille is exhibiting these side effects, please consult with your veterinarian to discuss different preventative options. Multidrug Sensitivity (MDR1) - CONDITION MDR1 - GENE NAME Sensitivity to certain classes of drugs, notably the parasiticide ivermectin, as well as certain gastroprotectant and anti-cancer medications, occurs in dogs with mutations in the MDR1 gene. Symptoms can range from vomiting and diarrhea to lethargy, seizures, or coma. MDR1 mutations are particularly common in herding breeds including Australian Shepherds, Collies, and Border Collies, though many other dog breeds are affected. Please note that the dosage of problem drugs in commercially available heartworm, flea, and tick preventatives should not cause symptoms in MDR1 dogs.

2 VON WILLEBRAND DISEASE TYPE II CHROMOSOME 27 Regency's Golden American Reveille has two healthy alleles at VWF. Von Willebrand Disease Type II (VWF Exon 28) - CONDITION VWF Exon 28 - GENE NAME Coagulopathies represent a broad category of diseases that affect blood clotting, which can lead to symptoms such as easy bruising or bleeding. Dogs with coagulopathies are often at risk for excessive bleeding during surgical procedures; your veterinarian should be informed so that appropriate blood products are at hand in case a transfusion is required. Affected dogs may also require special measures during routine veterinary procedures, and close monitoring during their daily lives. If informed of your dog's condition early, you and your veterinarian can begin taking precautionary measures now. Embark screens for 10 different mutations associated with coagulopathies. These include Hemophilia A and B and von Willebrand Disease, three of the most common inherited coagulopathies in dogs. As well as the precautionary methods described above, an emerging potential treatment for some coagulopathies include protein replacement therapy and gene therapy for a number of coagulopathies. Note that this mutation has been shown to be linked to, but not causative for, Type II von Willebrand Disease (vwd) in German Shorthaired Pointers and related breeds. This mutation has been identified in other breeds by Embark and others and does not appear to associate with Type II vwd risk in any other breed beyond the German Pointer breeds. vwd causes easy bruising and excessive bleeding from small cuts and nicks; you may also observe blood in your dog's stool or urine. Affected dogs are also at risk for excessive bleeding during surgery. Von Willebrand Factor is exposed on tissue surfaces upon tissue injury, where it is recognized by platelets and other clotting factors, thus triggering the clotting cascade. vwd is characterized into three types based on clinical severity, serum levels of vwf, and vwf multimer composition. Dogs with Type II vwd have low serum vwf, reduced high molecular weight vwf multimers, and mild to moderate clinical signs. Carrier PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 9 Regency's Golden American Reveille has two healthy alleles at PRCD. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Progressive Rod-Cone Degeneration (PRCD Exon 1) - CONDITION PRCD Exon 1 - GENE NAME INHERITANCE TYPE Recessive

3 This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. A late-onset form of PRA resulting from a mutation in the PRCD gene has been observed in many breeds and is inherited in an autosomal recessive manner. PRIMARY LENS LUXATION CHROMOSOME 3 Regency's Golden American Reveille has two healthy alleles at ADAMTS17. Please keep in mind that lens luxation can occur secondary to a number of conditions including glaucoma or trauma; regular veterinary checkups are the best way to monitor and maintain Regency's Golden American Reveille's healthy vision. In addition, this mutation does not explain cases of primary lens luxation in all breeds. Primary Lens Luxation (ADAMTS17) - CONDITION ADAMTS17 - GENE NAME INHERITANCE TYPE - Additive This surgically correctable condition causes the lens to spontaneously detach from its normal residence within the pupil, leading to reduced visual acuity and irritation to the surrounding tissues. The lens is suspended within the pupil by numerous small fibers that stretch between it and a ring of muscle within the iris (which allows your pupil to dilate and shrink to accommodate light). If these fibers rupture, the lens essentially falls out of the pupil. You can visually appreciate the lens luxation by peeking in your dog's pupil: almost always, the dislodged lens can be seen as a clear half moon either in front of or in back of the iris. If diagnosed early, PLL can be surgically corrected with few complications. Please note that while Embark tests for PLL, which has a known genetic basis, secondary lens luxation can be caused by a number of conditions including trauma, glaucoma, or certain metabolic diseases.

4 HYPERURICOSURIA AND HYPERURICEMIA OR UROLITHIASIS CHROMOSOME 3 Regency's Golden American Reveille has two healthy alleles at SLC2A9 and is unlikely to develop this form of urolithiasis. Please keep in mind that uroliths can form due to a number of factors: genetics is just one of them. Regular veterinary checkups where Regency's Golden American Reveille's urinary health can be evaluated is the best way to avoid Regency's Golden American Reveille developing other common forms of urolithiasis. Hyperuricosuria And Hyperuricemia Or Urolithiasis (SLC2A9) - CONDITION SLC2A9 (Exon 5) - GENE NAME This condition causes kidney and bladder stones composed of urate; if caught early, it is responsive to dietary management. Uric acid is an intermediate of purine metabolism. In most dogs, uric acid is converted to allantoin, an inert substance that is then excreted in the urine. Dogs with HUU have defects in the pathway that converts uric acid to allantoin. As such, uric acid builds up, crystallizes and forms urate stones in the kidney and bladder. While hyperuricemia in other species (including humans) can lead to painful conditions such as gout, dogs do not develop systemic signs of hyperuricemia. Urate stones are invisible on X-rays and must be diagnosed by a veterinarian via ultrasound or urine sediment analysis. If left undiagnosed, bladder stones can lead to urinary obstruction, which can be life threatening. DEGENERATIVE MYELOPATHY CHROMOSOME 31 Regency's Golden American Reveille has two healthy alleles at SOD1 and is unlikely to develop DM due to mutations in this gene. Degenerative Myelopathy (SOD1A) - CONDITION SOD1 - GENE NAME A disease of mature dogs, this is a progressive degenerative disorder of the spinal cord that can cause muscle wasting and gait abnormalities. Affected dogs do not usually show signs until they are at least eight years old, where the first signs of neural degeneration appears in the nerves that innervate the hind limbs. You may notice your dog scuffing the tops of his or her hind paws, or walking with a hesitant, exaggerated gait. In advanced cases, lower motor neurons are also affected leading to weakness or nearparalysis of all four legs and widespread muscle wasting. Given the advanced age at the time of onset, the treatment for DM is aimed towards making your dog comfortable in his or her old age and include lifestyle changes and physical therapy. All known predisposing mutations for DM lie in the SOD1 gene, and have been identified in many breeds including the Boxer, Pembroke Welsh Corgi, German Shepherd Dog, Rhodesian Ridgeback, Chesapeake Bay Retriever, and Bernese Mountain Dog. SOD1 codes

5 superoxide dismutase, an enzyme important in neutralizing free radicals and reactive oxygen species, both of which are produced as byproduct of cell metabolism. If not neutralized, these are injurious to the cell and will cause premature cell death. The first system to show effects of this is the nervous system given the highly specialized and delicate nature of these cells. Please note that these mutations are reported to have incomplete penetrance: that is, while a dog with two copies of this mutation has a much greater chance of developing DM than a dog with one copy of the mutation, or none at all, other genetic and environmental factors will also contribute to whether your dog develops DM. DILATED CARDIOMYOPATHY CHROMOSOME 14 Regency's Golden American Reveille has two healthy alleles at PDK4. Dilated Cardiomyopathy (PDK4) - CONDITION PDK4 - GENE NAME INHERITANCE TYPE- Dominant The most common acquired heart disease of dogs, this is a progressive disease of the heart ventricles: early diagnosis and treatment is key. The ventricles are the heavily muscled chambers that pump blood away from the heart. In DCM, the ventricles gradually lose muscle mass, leading to ventricular dilation, loss of heart contractility and an inability to pump oxygenated blood to the body. DCM typically presents in adult dogs in the end stages of the disease, when the heart is on its last legs. Signs include weakness, cold toes and ears, blue-grey gums and tongue, and respiratory distress: all signs of heart failure. Once a DCM dog comes to the vet, DCM can be diagnosed using specialized tests to evaluate the shape and activity fo the heart muscle. Important note about the PDK4 mutation (also known as DCM1): The vast majority of research exploring the genetics of DCM has been performed on purebred American Dobermans, a high risk population for DCM. Even in the Doberman, DCM1 is incompletely penetrant, meaning that while having one or two copies of this mutation is thought to confer some increased risk of developing DCM, it is by no means predictive of disease. DCM is a highly complex disease that is modulated by many genetic factors, most unknown. In addition, Embark and others have identified this mutation in multiple breeds, including breeds where DCM is not a common disease. The impact of this mutation in these breeds is unknown: Embark hopes to change this. EXERCISE-INDUCED COLLAPSE CHROMOSOME 9 Regency's Golden American Reveille has two healthy alleles at DNM1. Exercise-Induced Collapse (DNM1) - CONDITION DNM1 - GENE NAME

6 First characterized in field-trial lines of Labrador Retriever dogs, this muscle disorder can cause episodes of muscle weakness and sometimes collapse; after recovering, most dogs are perfectly normal and eager to get back to work. While most dogs appear dazed or confused after an episode, most return to normal quickly. Dogs are otherwise normal and healthy, though some severely affected dogs have died during an episode. The factors determining the severity of an episode on a given day or in a given dog is unknown. EIC has been linked to a mutation in the DNM1 gene, which codes for the protein dynamin. In the neuron, dynamin trucks neurotransmitter-filled vesicles from the cell body, where they are generated, to the dendrites. It is hypothesized in dogs affected with EIC, the mutation in DNM1 disrupts efficient neurotransmitter release, leading to a cessation in signalling and EIC. S CONGENITAL HYPOTHYROIDISM CHROMOSOME 17 Regency's Golden American Reveille has two healthy alleles at TPO and is unlikely to be congenitally hypothyroid. Please keep in mind that hypothyroidism can be acquired, especially in older dogs. The mutations we test for do guarantee that Regency's Golden American Reveille will not develop acquired hypothyroidism later in life: regular veterinary checkups and monitoring of Regency's Golden American Reveille's health is key to catching and treating the first signs of age-related disease. Congenital Hypothyroidism (TPO Variant 1) - CONDITION TPO - GENE NAME This a medically manageable condition that arises from an inherent inability to produce the hormone thyroxine. Congenitally hypothyroid pups are usually lethargic and overweight with a characteristic tragic facial expression due to increased water retention in the facial folds. Abdominal hair loss, as well as a characteristic goiter,which is actually an enlarged thyroid gland attempting to produce thyroxine (to no avail), are also common. Thyroxine plays a role in early life skeletal and nervous system development, so congenitally hypothyroid pups can present with dwarfism of the long bones and spine as well as delayed mental development. Hypothyroidism is a lifetime condition and can be managed medically with thyroxine supplementation. In rare cases of untreated hypothyroidism, dogs can enter a condition known as myxedema coma, where lethargy can progress to a comatose state complete with a reduced heart rate, breathing rate, and low body temperature. This is an emergency situation that requires intensive care but can be prevented with early diagnosis and treatment. S SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME 29 Regency's Golden American Reveille has two healthy alleles at PRKDC. Severe Combined Immunodeficiency (PRKDC) - CONDITION PRKDC - GENE NAME

7 As can be surmised from the name, this is a deficiency of multiple immune components: affected dogs require close monitoring for signs of infection, and should not be administered modified live vaccines. SCID pups cannot produce functional B-lymphocytes, the cells responsible for producing antibodies and long-term memory of infection, as well as T-lymphocytes, which can act to destroy immune cells themselves as well as direct other immune cells to do their job. In the absence of a functional immune system, they are extremely susceptible to infections contracted soon after weaning or from administration of modified live vaccines, which rely on a competent immune system to confer immunity. S SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME 18 Regency's Golden American Reveille has two healthy alleles at RAG1. Severe Combined Immunodeficiency (RAG1) - CONDITION RAG1 - GENE NAME As can be surmised from the name, this is a deficiency of multiple immune components: affected dogs require close monitoring for signs of infection, and should not be administered modified live vaccines. SCID pups cannot produce functional B-lymphocytes, the cells responsible for producing antibodies and long-term memory of infection, as well as T-lymphocytes, which can act to destroy immune cells themselves as well as direct other immune cells to do their job. In the absence of a functional immune system, they are extremely susceptible to infections contracted soon after weaning or from administration of modified live vaccines, which rely on a competent immune system to confer immunity. S X-LINKED SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME X Regency's Golden American Reveille has a healthy genotype at IL2RG. X-Linked Severe Combined Immunodeficiency (IL2RG Variant 1) - CONDITION IL2RG Exon 1 - GENE NAME INHERITANCE TYPE - X-Linked Recessive As can be surmised from the name, this is a deficiency of multiple immune components: affected dogs require close monitoring for signs of infection, and should not be administered modified live vaccines. SCID pups cannot produce functional B-lymphocytes, the cells responsible for producing antibodies and

8 long-term memory of infection, as well as T-lymphocytes, which can act to destroy immune cells themselves as well as direct other immune cells to do their job. In the absence of a functional immune system, they are extremely susceptible to infections contracted soon after weaning or from administration of modified live vaccines, which rely on a competent immune system to confer immunity. S X-LINKED SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME X Regency's Golden American Reveille has a healthy genotype at IL2RG. X-Linked Severe Combined Immunodeficiency (IL2RG Variant 2) - CONDITION IL2RG - GENE NAME INHERITANCE TYPE - X-Linked Recessive As can be surmised from the name, this is a deficiency of multiple immune components: affected dogs require close monitoring for signs of infection, and should not be administered modified live vaccines. SCID pups cannot produce functional B-lymphocytes, the cells responsible for producing antibodies and long-term memory of infection, as well as T-lymphocytes, which can act to destroy immune cells themselves as well as direct other immune cells to do their job. In the absence of a functional immune system, they are extremely susceptible to infections contracted soon after weaning or from administration of modified live vaccines, which rely on a competent immune system to confer immunity. S PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 3 Regency's Golden American Reveille has two healthy alleles at PDE6B. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Rod-Cone Dysplasia, Rcd1 (PDE6B Exon 21 Irish Setter Variant) - CONDITION PDE6B Exon 21 - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease:

9 most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. Rod-Cone Dysplasia is distinct from other forms of PRA in that it has a developmental aspect to its disease process. The rod cells of pups with rod-cone dystrophy are morphologically abnormal, hence the name dysplasia rather than metabolically abnormal, as indicated in dystrophy. Some studies indicate that the abnormalities in rod cell morphology and function arise after birth. PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 4 Regency's Golden American Reveille has two healthy alleles at PDE6A. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Rod-Cone Dysplasia, Rcd3 (PDE6A) - CONDITION PDE6A - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian.

10 Rod-Cone Dysplasia is distinct from other forms of PRA in that it has a developmental aspect to its disease process. The rod cells of pups with rod-cone dystrophy are morphologically abnormal, hence the name dysplasia rather than metabolically abnormal, as indicated in dystrophy. Some studies indicate that the abnormalities in rod cell morphology and function arise after birth. PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 13 Regency's Golden American Reveille has two healthy alleles at CNGA1. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) (CNGA1 Exon 9) - CONDITION CNGA1 Exon 9 - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. PRA caused by mutations in the CNGA1 gene has been described in Shetland Sheepdogs. Affected dogs are reported to show symptoms around 3-5 years of age.

11 PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 9 Regency's Golden American Reveille has two healthy alleles at PRCD. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Progressive Rod-Cone Degeneration (PRCD Exon 1) - CONDITION PRCD Exon 1 - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. A late-onset form of PRA resulting from a mutation in the PRCD gene has been observed in many breeds and is inherited in an autosomal recessive manner. PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 2 Regency's Golden American Reveille has two healthy alleles at CNGB1. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) (CNGB1) - CONDITION CNGB1 - GENE NAME

12 This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. PRA caused by a mutation in CNGB1 has been described in Papillons and Phalenes. The age of onset is highly variable with this form of PRA, but dogs typicaly have complete loss of vision by by seven years of age. PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 25 Regency's Golden American Reveille has two healthy alleles at SAG. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long-term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) (SAG) - CONDITION SAG - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to

13 go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. An adult-onset form of PRA caused by a mutation in the SAG gene has been described in the Basenji. The age of onset is highly variable; anywhere from 2 to 7 years old has been reported. This mutation is inherited in an autosomal recessive manner with incomplete penetrance; that is, some Basenjis with two copies of this mutation do not develop PRA, suggesting that at least in the Basenji this is a disease involving the interactions of many genes. PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 8 Regency's Golden American Reveille has two healthy alleles at TTC8. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Golden Retriever PRA 2 (TTC8) - CONDITION TTC8 Exon 8 - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian.

14 A late-onset form of PRA caused by a mutation in the TTC8 gene has been reported in the Golden Retriever and the Lhasa Apso. S PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 3 Regency's Golden American Reveille has two healthy alleles at PDE6B. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Cone-Rod Dystrophy 1, Crd1 (PDE6B) - CONDITION PDE6B - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. PRA, Cone-Rod Dystrophy (PRA-crd) is distinct from other forms of PRA in that it is characterized by an early loss of the cone cells, leading to a loss of day vision before a loss of night vision. It can be caused by a number of mutations in different genes, many of which affect retinal cell development and maintenance. In the American Pitbull Terrier and the American Staffordshire Terrier, PRA-crd has been mapped to a mutation in the PDE6B gene. This mutation is inherited in an autosomal recessive manner; that is, a dog requires two copies of the mutation to show signs of the disease. PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 33

15 Regency's Golden American Reveille has two healthy alleles at IQCB1. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Cone-Rod Dystrophy 2, Crd2 (IQCB1) - CONDITION IQCB1 - GENE NAME This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. PRA, Cone-Rod Dystrophy (PRA-crd) is distinct from other forms of PRA in that it is characterized by an early loss of the cone cells, leading to a loss of day vision before a loss of night vision. It can be caused by a number of mutations in different genes, many of which affect retinal cell development and maintenance. In the American Pitbull Terrier and the American Staffordshire Terrier, PRA-crd has been mapped to a mutation in the IQCB1 gene. This mutation is inherited in an autosomal recessive manner; that is, a dog requires two copies of the mutation to show signs of the disease. PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 15 Regency's Golden American Reveille has two healthy alleles at RPGRIP1. Keep in mind that eyesight can deteriorate with age for non-genetic causes: please consult with your veterinarian for a long term health and monitoring plan as your pup gets older. Progressive Retinal Atrophy (PRA) Cone-Rod Dystrophy, Crd4/Cord1 (RPGRIP1) - CONDITION RPGRIP1 (Exon 2) - GENE NAME

16 This retinal disease causes progressive, nonpainful vision loss. The retina contains the cells, photoreceptors, that collect information about light: that is, they are the very beginning of how we see. There are two types of photoreceptors: rods, which gather information about light intensity and are the major contributors to night vision, and cones, which distinguish color and are the major contributors to day vision. In nearly all forms of PRA, the rod cells are affected first, leading to night blindness. They are followed by the cone cells, leading to day blindness. The mechanisms by which the photoreceptors degenerate vary depending on the specific mutation that causes PRA. However, the readout is the same: the dog experiences a slow loss of vision, often leading to complete blindness. PRA is a subtle disease: most owners do not even know that their dog has gone blind--you may notice that your dog is reluctant to go down the stairs, or bumping into door frames or corners, or taking a very long time to fetch a ball or toy. A peek at your dog s eyes in bright light may also reveal a sluggish pupillary constriction, because the retina is no longer telling your pupils that it is letting in too much light. Diagnosis of PRA can be made by your veterinarian, who can examine the retina s appearance with ophthalmoscope, or can query its electrical activity with an electroretinogram. Because of the slow progression of PRA, most dogs adapt very well to their condition and remain comfortable in familiar surroundings like their home, backyard, and daily walk route. Over time, many dogs with PRA can develop cataracts. This is thought to be due to buildup of reactive oxygen species and other toxic metabolites released from the dying retinal cells. This can lead to other ophthalmologic conditions and requires close monitoring in consultation with your veterinarian. PRA, Cone-Rod Dystrophy (PRA-crd) is distinct from other forms of PRA in that it is characterized by an early loss of the cone cells, leading to a loss of day vision before a loss of night vision. It can be caused by a number of mutations in different genes, many of which affect retinal cell development and maintenance. A mutation in the RPGRIP1 gene has been identified as the causative mutation for PRA-crd in many breeds. This mutation is inherited in an autosomal recessive manner; that is, a dog requires two copies of the mutation to show signs of the disease. MUSCULAR DYSTROPHY CHROMOSOME X Regency's Golden American Reveille has two healthy alleles at DMD. Muscular Dystrophy (DMD Golden Retriever Variant) - CONDITION DMD - GENE NAME INHERITANCE TYPE - X-Linked Recessive Characterized by non-painful muscle weakness and wasting, early diagnosis and supportive treatment can slow the pace of this progressive muscle disease. All known mutations for muscular dystrophy lie in the DMD gene, which codes for the protein dystrophin. Dystrophin is an essential part of a protein complex that specifically acts to provide strength and protection to muscle fibers: it does this by anchoring the muscle fiber to its surrounding structures, ensuring that it will move with the rest of the muscle and providing additional support when it contracts. Dogs affected with MD have abnormally low levels of functional dystrophin, leading to muscle fiber damage, progressive muscle wasting, and weakness. The

17 most dramatic symptoms include difficulty walking and visible muscle wasting over the back and legs, the disease will also affect the muscles that control swallowing and breathing. Because MD is inherited in a recessive manner and dystrophin is located on the X chromosome, males are twice as likely as females to exhibit the disease. Current treatments for muscular dystrophy include steroid treatment, which can slow the progression of the disease, but there is currently no cure. However, much research has gone into gene therapy: researchers have recently demonstrated that supplementing the defective dystrophin gene of a dog with MD with a new, smaller form of dystrophin (known as microdystrophin) can fully substitute for full sized dystrophin. ICHTHYOSIS, EPIDERMOLYTIC HYPERKERATOSIS CHROMOSOME 9 Regency's Golden American Reveille has two healthy alleles at KRT10. Ichthyosis, Epidermolytic Hyperkeratosis (KRT10) - CONDITION KRT10 (Intron 5) - GENE NAME This skin disorder gets its name from the thick, darkly pigmented scales of skin ( ichthys is Greek for fish ) that affected dogs display on their noses, paw pads, and muzzles. Over time these scales can get so thick that they can crack and cause fissures, leading to considerable discomfort. Ichthyotic dogs also typically have large, greasy flakes of dandruff, but unlike dogs with dry skin, they aren t itchy. There is no definitive treatment for ichthyosis: typically, ichthyotic dogs are maintained on a continuous treatment of mild anti-dandruff shampoos and moisturizing rinses. Carrier ICHTHYOSIS CHROMOSOME 12 Regency's Golden American Reveille has two healthy alleles at PNPLA1. Ichthyosis (PNPLA1) - CONDITION PNPLA1 (Exon 8) - GENE NAME This skin disorder gets its name from the thick, darkly pigmented scales of skin ( ichthys is Greek for fish ) that affected dogs display on their noses, paw pads, and muzzles. Over time these scales can get so thick that they can crack and cause fissures, leading to considerable discomfort. Ichthyotic dogs also typically have large, greasy flakes of dandruff, but unlike dogs with dry skin, they aren t itchy. There is no definitive treatment for ichthyosis: typically, ichthyotic dogs are maintained on a continuous treatment of mild anti-dandruff shampoos and moisturizing rinses.

18 ICHTHYOSIS CHROMOSOME 9 Regency's Golden American Reveille has two healthy alleles at SLC27A4. Ichthyosis (SLC27A4) - CONDITION SLC27A4 - GENE NAME This skin disorder gets its name from the thick, darkly pigmented scales of skin ( ichthys is Greek for fish ) that affected dogs display on their noses, paw pads, and muzzles. Over time these scales can get so thick that they can crack and cause fissures, leading to considerable discomfort. Ichthyotic dogs also typically have large, greasy flakes of dandruff, but unlike dogs with dry skin, they aren t itchy. There is no definitive treatment for ichthyosis: typically, ichthyotic dogs are maintained on a continuous treatment of mild anti-dandruff shampoos and moisturizing rinses. All other health conditions tested Regency's Golden American Reveille tested CLEAR for all these conditions: Multidrug Sensitivity (MDR1) (Chromosome 14) P2RY12 Defect (P2RY12) (Chromosome 23) Factor IX Deficiency, Hemophilia B (F9 Exon 7, Terrier Variant) (Chromosome X) Factor IX Deficiency, Hemophilia B (F9 Exon 7, Rhodesian Ridgeback Variant) (Chromosome X) Factor VII Deficiency (F7 Exon 5) (Chromosome 22) Factor VIII Deficiency, Hemophilia A (F8 Exon 10, Boxer Variant) (Chromosome X) Factor VIII Deficiency, Hemophilia A (F8 Exon 11, Shepherd Variant 1) (Chromosome X) Factor VIII Deficiency, Hemophilia A (F8 Exon 1, Shepherd Variant 2) (Chromosome X) Thrombopathia (RASGRP2 Exon 5, Basset Hound Variant) (Chromosome 18) Thrombopathia (RASGRP2 Exon 8) (Chromosome 18) Thrombopathia (RASGRP2 Exon 5, American Eskimo Dog Variant) (Chromosome 18) Von Willebrand Disease Type II (VWF Exon 28) (Chromosome 27) Von Willebrand Disease Type III (VWF Exon 4) (Chromosome 27) Von Willebrand Disease Type I (VWF) (Chromosome 27) Canine Leukocyte Adhesion Deficiency Type III (FERMT3) (Chromosome 18) Congenital Macrothrombocytopenia (TUBB1 Exon 1, Cavalier King Charles Spaniel Variant) (Chromosome 24) Canine Elliptocytosis (SPTB Exon 30) (Chromosome 8) Cyclic Neutropenia, Gray Collie Syndrome (AP3B1 Exon 20) (Chromosome 31) Glanzmann's Thrombasthenia Type I (ITGA2B Exon 13) (Chromosome 9) Glanzmann's Thrombasthenia Type I (ITGA2B Exon 12) (Chromosome 9) May-Hegglin Anomaly (MYH9) (Chromosome 10) Prekallikrein Deficiency (KLKB1 Exon 8) (Chromosome 16) Pyruvate Kinase Deficiency (PKLR Exon 5) (Chromosome 7) Pyruvate Kinase Deficiency (PKLR Exon 7 Labrador Variant) (Chromosome 7) Pyruvate Kinase Deficiency (PKLR Exon 7 Pug Variant) (Chromosome 7) Pyruvate Kinase Deficiency (PKLR Exon 7 Beagle Variant) (Chromosome 7) Pyruvate Kinase Deficiency (PKLR Exon 10) (Chromosome 7)