MYSTIC DANNIKA OF EVANS

Transcription

1 MYSTIC DANNIKA OF EVANS Genetic Vet Report by embarkvet.com Test Date: April 17th, 2018 Customer-supplied information Owner Name: Mystic Danes Dog Name: Mystic Dannika of Evans Sex: Female (intact) Breed type: Purebred Breed: Great Dane Microchip: **** 0 AT RISK Summary 0 CARRIER Not At Risk Good news! Mystic Kanaan of Night Sky did not test positive for any of the genetic diseases that Embark screens for. Not A Carrier Good news! Mystic Kanaan of Night Sky is not a carrier for any of the genetic diseases that Embark tests for. Common conditions Good news! Mystic Kanaan of Night Sky tested clear for 8 other common genetic diseases that Embark tests for. MULTIDRUG SENSITIVITY CHROMOSOME 14 Test Result Mystic Kanaan of Night Sky 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 Mystic Kanaan of Night Sky is exhibiting these side effects, please consult with your veterinarian to discuss different preventative options. Multidrug Sensitivity (MDR1) - CONDITION MDR1 - GENE NAME CODOMINANT- INHERITANCE TYPE

2 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. VON WILLEBRAND DISEASE TYPE II CHROMOSOME 27 Mystic Kanaan of Night Sky 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.

3 PROGRESSIVE RETINAL ATROPHY (PRA) CHROMOSOME 9 Mystic Kanaan of Night Sky 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 Recessive - INHERITANCE TYPE 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 Mystic Kanaan of Night Sky 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. Primary Lens Luxation (ADAMTS17) - CONDITION ADAMTS17 - GENE NAME ADDITIVE - INHERITANCE TYPE

4 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. HYPERURICOSURIA AND HYPERURICEMIA OR UROLITHIASIS CHROMOSOME 3 Mystic Kanaan of Night Sky 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 Mystic Kanaan of Night Sky's urinary health can be evaluated is the best way to avoid Mystic Kanaan of Night Sky 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 Mystic Kanaan of Night Sky 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

5 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 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 Mystic Kanaan of Night Sky has two healthy alleles at PDK4. Dilated Cardiomyopathy (PDK4) - CONDITION PDK4 - GENE NAME DOMINANT - INHERITANCE TYPE 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. If you have recently had your dog's heart evaluated by your veterinarian, please us at howdy@embarkvet.com.

6 EXERCISE-INDUCED COLLAPSE CHROMOSOME 9 Mystic Kanaan of Night Sky has two healthy alleles at DNM1. Exercise-Induced Collapse (DNM1) - CONDITION DNM1 - GENE NAME 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. Other Conditions: of 157 Mystic Kanaan of Night Sky is clear of 157 other genetic diseases that Embark tests for. **Some of the most important tests, or those common to Great Danes are explained in detail. The rest of the DNA tests are just listed by name. VON WILLEBRAND DISEASE TYPE I CHROMOSOME 27 Mystic Kanaan of Night Sky has two healthy alleles at VWF. Von Willebrand Disease Type I (VWF) - CONDITION VWF - 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

7 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. Von Willebrand Disease (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 I vwd have low vwf levels, normal vwf multimer composition, and mild to moderate clinical signs. VON WILLEBRAND DISEASE TYPE III CHROMOSOME 27 Mystic Kanaan of Night Sky has two healthy alleles at VWF. Von Willebrand Disease Type III (VWF Exon 4) - CONDITION VWF Exon 4 - 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. Von Willebrand Disease (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. Type III vwf is characterized by total loss of serum vwf and severe clinical signs

8 CONGENITAL HYPOTHYROIDISM CHROMOSOME 17 Mystic Kanaan of Night Sky 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 Mystic Kanaan of Night Sky will not develop acquired hypothyroidism later in life: regular veterinary checkups and monitoring of Mystic Kanaan of Night Sky'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. SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME 29 Mystic Kanaan of Night Sky has two healthy alleles at PRKDC. Severe Combined Immunodeficiency (PRKDC) - CONDITION PRKDC - 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.

9 SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME 18 Mystic Kanaan of Night Sky 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. X-LINKED SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME X Mystic Kanaan of Night Sky has a healthy genotype at IL2RG. X-Linked Severe Combined Immunodeficiency (IL2RG Variant 1) - CONDITION IL2RG Exon 1 - GENE NAME X-Linked Recessive - INHERITANCE TYPE 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.

10 X-LINKED SEVERE COMBINED IMMUNODEFICIENCY CHROMOSOME X Mystic Kanaan of Night Sky has a healthy genotype at IL2RG. X-Linked Severe Combined Immunodeficiency (IL2RG Variant 2) - CONDITION IL2RG - GENE NAME X-Linked Recessive - INHERITANCE TYPE 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. MACULAR CORNEAL DYSTROPHY (MCD) CHROMOSOME 5 Mystic Kanaan of Night Sky has two healthy alleles at CHST6. Macular Corneal Dystrophy (MCD) (CHST6) - CONDITION CHST6 - GENE NAME A disease of middle-aged dogs, MCD was first characterized in the Labrador Retriever. Affected dogs begin to show clouding of the eyes and visual impairment due to abnormal corneal accumulation of complex carbohydrates called glycosaminoglycans. Currently there is no cure for canine MCD, though in humans, corneal transplant is the gold standard of treatment. POLYCYSTIC KIDNEY DISEASE CHROMOSOME 6 Mystic Kanaan of Night Sky has two healthy alleles at PKD and is unlikely to develop polycystic kidney disease caused by mutations in this gene. Please keep in mind that as Mystic Kanaan of Night Sky ages, kidney health can decline: the best way to keep Mystic Kanaan of Night Sky healthy is routine vet checkups where his or her kidney health can be evaluated.

11 Polycystic Kidney Disease (PKD1) - CONDITION PKD1 (Exon 29) - GENE NAME DOMINANT - INHERITANCE TYPE This is adult-onset disease causes progressive loss of kidney function. Cysts are abnormal, fluid filled structures that arise from the kidney cells themselves. As they grow, take up functional space within the kidney. Signs of PKD are reflective of the cysts expanding: the kidney capsule is stretched, leading to severe abdominal pain, and kidney function is compromised, where you may notice your dog drinking and urinating excessively. Severe loss of kidney function is characterized by vomiting, lethargy, neurologic behavior, and the inability to produce urine (anuria). AUTOSOMAL RECESSIVE HEREDITARY NEPHROPATHY, FAMILIAL NEPHROPATHY CHROMOSOME 25 Mystic Kanaan of Night Sky has two healthy alleles at COL4A4. Autosomal Recessive Hereditary Nephropathy, Familial Nephropathy (COL4A4 Exon 3) - CONDITION COL4A4 (Exon 3) - GENE NAME This condition causes inappropriate loss of protein in the urine, which leads to muscle wasting, abnormal fluid accumulation in the skin and limbs, and excessive thirst and urination; if diagnosed early it can be managed with dietary changes and close monitoring. Certain parts of the kidney act as a sieve through which ions, small molecules like urea, and water are filtered out of the blood into the urine. Normally, cells and large molecules like proteins are excluded by the sieve and are retained in circulation. In PLN, the sieve is compromised, and protein moves in the urine. Protein retention at the level of the kidney is essential for maintaining lean body weight, blood volume, and blood pressure. Animals with PLN exhibit muscle wasting, abnormal accumulation of fluids in the tissue (edema), and excessive thirst and urination. Loss of certain clotting proteins also puts PLN dogs at high risk of thromboembolism. Finally, huge loads of protein are toxic to the kidney, so dogs eventually show signs of renal failure, which include vomiting, inappetance, lethargy, and reduced urine production (anuria). Current therapies for PLN are aimed at reducing the protein load on the kidney and fighting the toxic effects of protein wasting--these include prescription diets, reducing blood flow to the kidneys, and anti-inflammatory therapy. However, there is no definitive treatment for PLN besides dialysis and/or kidney transplant. Some efforts in gene therapy have been made to supplement PLN animals with the functional protein that they lack, but these are far from being used in practice. It is important to note that PLN can be secondary to a variety of diseases. In the absence of genetic testing, breed disposition or family history of PLN, your veterinarian will need to rule out other causes of PLN with a series of diagnostic tests.

12 BENIGN FAMILIAL JUVENILE EPILEPSY, REMITTING FOCAL EPILEPSY CHROMOSOME 3 Mystic Kanaan of Night Sky has two healthy alleles at LGI2. Benign Familial Juvenile Epilepsy, Remitting Focal Epilepsy (LGI2) - CONDITION LGI2 (Exon 8) - GENE NAME A disorder of young dogs, this causes intermittent seizures that resolve with age. Affected dogs can begin experiencing seizures of varying frequency, duration, and severity, ranging from simple focal seizures where the dog is tremoring but still able to walk, eat, and respond to stimulus to complete immobilization and loss of consciousness. Puppies appear normal between episodes, though those with severe seizures can display an abnormal, uncoordinated gait after an episode. Treatment for BFJE is usually supportive; dogs typically grow out of the disease and suffer no ill effects later in life. This condition was first identified in the Lagotto Romagnolo, where the causative mutation lies in the LGI2 enzyme. LGI2 codes for an enzyme involved in neuronal circuit remodeling, a normal and necessary process that occurs in puppyhood. INHERITED MYOPATHY OF GREAT DANES CHROMOSOME 19 Mystic Kanaan of Night Sky has two healthy alleles at BIN1. Inherited Myopathy Of Great Danes (BIN1) - CONDITION BIN1 - GENE NAME This muscle wasting disease causes young dogs to present with weakness, unsteady gait, generalized muscle wasting, and exercise intolerance. The severity of the disease can vary between individuals of the same litter, with some animals being so severely affected that euthanasia is elected and others maintaining a good quality of life after symptoms have stabilized. IMGD stems from a mutation in the BIN1 gene, which codes for a protein that controls cell membrane remodeling: this is especially important for muscle development and growth. Loss of BIN1 causes prevents muscle cells from differentiating correctly, ultimately leading to muscle malfunction and damage in the growing dog. Currently there is no treatment for IMGD; mildly to moderately affected dogs usually stabilize by two years of age and enjoy a normal lifespan. Mystic Kanaan of Night Sky 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)

13 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) Trapped Neutrophil Syndrome (VPS13B) (Chromosome 13) Ligneous Membranitis (PLG) (Chromosome 1) Congenital Hypothyroidism (TPO Variant 1) (Chromosome 17) Complement 3 (C3) deficiency (C3) (Chromosome 20) Severe Combined Immunodeficiency (PRKDC) (Chromosome 29) Severe Combined Immunodeficiency (RAG1) (Chromosome 18) X-linked Severe Combined Immunodeficiency (IL2RG Variant 1) (Chromosome X) X-linked Severe Combined Immunodeficiency (IL2RG Variant 2) (Chromosome X) Progressive Retinal Atrophy (PRA) Rod-cone dysplasia, rcd1 (PDE6B Exon 21 Irish Setter Variant) (Chromosome 3) Progressive Retinal Atrophy (PRA) Rod-cone dysplasia, rcd1a (PDE6B Exon 21 Sloughi Variant) (Chromosome 3) Progressive Retinal Atrophy (PRA) Rod-cone dysplasia, rcd3 (PDE6A) (Chromosome 4) Progressive Retinal Atrophy (PRA) (CNGA1 Exon 9) (Chromosome 13) Progressive Retinal Atrophy (PRA) Progressive rod-cone degeneration (PRCD Exon 1) (Chromosome 9) Progressive Retinal Atrophy (PRA) (CNGB1) (Chromosome 2) Progressive Retinal Atrophy (PRA) (SAG) (Chromosome 25) Progressive Retinal Atrophy (PRA) Golden Retriever PRA 2 (TTC8) (Chromosome 8) Progressive Retinal Atrophy (PRA) Cone-rod dystrophy 1, crd1 (PDE6B) (Chromosome 3) Progressive Retinal Atrophy (PRA) Cone-rod dystrophy 2, crd2 (IQCB1) (Chromosome 33) Progressive Retinal Atrophy (PRA) Cone-rod dystrophy, crd4/cord1 (RPGRIP1) (Chromosome 15) Collie Eye Anomaly, Choroidal Hypoplasia (NHEJ1) (Chromosome 37) Day blindness, Achromatopsia, Cone Degeneration (CNGB3 Exon 6) (Chromosome 29)

14 Achromatopsia (CNGA3 Exon 7 German Shepherd Variant) (Chromosome 10) Achromatopsia (CNGA3 Exon 7 Labrador Retriever Variant) (Chromosome 10) Autosomal Dominant Progressive Retinal Atrophy (RHO) (Chromosome 20) Canine Multifocal Retinopathy cmr1 (BEST1 Exon 2) (Chromosome 18) Canine Multifocal Retinopathy cmr2 (BEST1 Exon 5) (Chromosome 18) Canine Multifocal Retinopathy cmr3 (BEST1 Exon 10 Deletion) (Chromosome 18) Canine Multifocal Retinopathy cmr3 (BEST1 Exon 10 SNP) (Chromosome 18) Glaucoma Primary Open Angle Glaucoma (ADAMTS10 Exon 9) (Chromosome 20) Glaucoma Primary Open Angle Glaucoma (ADAMTS10 Exon 17) (Chromosome 20) Glaucoma Primary Open Angle Glaucoma (ADAMTS17 Exon 12) (Chromosome 3) Hereditary Cataracts, Early-Onset Cataracts, Juvenile Cataracts (HSF4 Exon 9 Boston Terrier Variant) (Chromosome 5) Hereditary Cataracts, Early-Onset Cataracts, Juvenile Cataracts (HSF4 Exon 9 Shepherd Variant) (Chromosome 5) Primary Lens Luxation (ADAMTS17) (Chromosome 3) Congenital stationary night blindness (RPE65) (Chromosome 6) Macular Corneal Dystrophy (MCD) (CHST6) (Chromosome 5) 2,8-Dihydroxyadenine (2,8-DHA) Urolithiasis (APRT) (Chromosome 5) Cystinuria Type I-A (SLC3A1) (Chromosome 10) Cystinuria Type II-A (SLC3A1) (Chromosome 10) Cystinuria Type II-B (SLC7A9) (Chromosome 1) Hyperuricosuria and Hyperuricemia or Urolithiasis (SLC2A9) (Chromosome 3) Polycystic Kidney Disease (PKD1) (Chromosome 6) Primary Hyperoxaluria (AGXT) (Chromosome 25) Protein Losing Nephropathy (NPHS1) (Chromosome 1) X-Linked Hereditary Nephropathy (COL4A5 Exon 35) (Chromosome X) Autosomal Recessive Hereditary Nephropathy, Familial Nephropathy (COL4A4 Exon 3) (Chromosome 25) Primary Ciliary Dyskinesia (CCDC39 Exon 3) (Chromosome 34) Congenital Keratoconjunctivitis Sicca and Ichthyosiform Dermatosis (CKCSID), Dry Eye Curly Coat Syndrome (FAM83H Exon 5) (Chromosome 13) X-linked Ectodermal Dysplasia, Anhidrotic Ectodermal Dysplasia (EDA Intron 8) (Chromosome X) Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND) (FLCN Exon 7) (Chromosome 5) Glycogen Storage Disease Type II, Pompe's Disease (GAA) (Chromosome 9) Glycogen Storage Disease Type Ia, Von Gierke Disease (G6PC) (Chromosome 9) Glycogen Storage Disease Type IIIa (GSD IIIa) (AGL) (Chromosome 6) Mucopolysaccharidosis Type IIIA, Sanfilippo Syndrome Type A (SGSH Exon 6 Variant 1) (Chromosome 9) Mucopolysaccharidosis Type IIIA, Sanfilippo Syndrome Type A (SGSH Exon 6 Variant 2) (Chromosome 9) Mucopolysaccharidosis Type VII, Sly Syndrome (GUSB Exon 5) (Chromosome 6) Mucopolysaccharidosis Type VII, Sly Syndrome (GUSB Exon 3) (Chromosome 6) Glycogen storage disease Type VII, Phosphofructokinase deficiency (PFKM Exon 21) (Chromosome 27) Glycogen storage disease Type VII, Phosphofructokinase deficiency (PFKM Exon 8) (Chromosome 27) Lagotto Storage Disease (ATG4D) (Chromosome 20) Neuronal Ceroid Lipofuscinosis 1 (PPT1 Exon 8) (Chromosome 15) Neuronal Ceroid Lipofuscinosis 2 (TPP1 Exon 4) (Chromosome 21) Neuronal Ceroid Lipofuscinosis 1 (ARSG Exon 2) (Chromosome 9)

15 Neuronal Ceroid Lipofuscinosis 1 (CLN5 Exon 4 Variant 1) (Chromosome 22) Neuronal Ceroid Lipofuscinosis 6 (CLN6 Exon 7) (Chromosome 30) Neuronal Ceroid Lipofuscinosis 8 (CLN8 Exon 2) (Chromosome 37) Neuronal Ceroid Lipofuscinosis (MFSD8) (Chromosome 19) Neuronal Ceroid Lipofuscinosis (CLN8) (Chromosome 37) Neuronal Ceroid Lipofuscinosis 10 (CTSD Exon 5) (Chromosome 18) Neuronal Ceroid Lipofuscinosis (CLN5 Exon 4 Variant 2) (Chromosome 22) Adult-Onset Neuronal Ceroid Lipofuscinosis (ATP13A2) (Chromosome 2) Gangliosidosis GM1 Gangliosidosis (GLB1 Exon 15 Shiba Inu Variant) (Chromosome 23) Gangliosidosis GM1 Gangliosidosis (GLB1 Exon 15 Alaskan Husky Variant) (Chromosome 23) Gangliosidosis GM1 Gangliosidosis (GLB1 Exon 2) (Chromosome 23) Gangliosidosis GM2 Gangliosidosis (HEXB Exon 3) (Chromosome 2) Gangliosidosis GM2 Gangliosidosis (HEXA) (Chromosome 30) Globoid Cell Leukodystrophy, Krabbe disease (GALC Exon 5) (Chromosome 8) Autosomal Recessive Amelogenesis Imperfecta (ENAM) (Chromosome 13) Persistent Mullerian Duct Syndrome (AMHR2) (Chromosome 27) Alaskan Husky Encephalopathy, Subacute Necrotizing Encephalomyelopathy (SLC19A3) (Chromosome 25) Alexander Disease (GFAP) (Chromosome 9) Cerebellar Abiotrophy, Neonatal Cerebellar Cortical Degeneration (SPTBN2) (Chromosome 18) Cerebellar Ataxia, Progressive Early-Onset Cerebellar Ataxia (SEL1L) (Chromosome 8) Cerebellar Hypoplasia (VLDLR) (Chromosome 1) Spinocerebellar Ataxia, Late-Onset Ataxia (CAPN1) (Chromosome 18) Spinocerebellar Ataxia with Myokymia and/or Seizures (KCNJ10) (Chromosome 38) Benign Familial Juvenile Epilepsy, Remitting Focal Epilepsy (LGI2) (Chromosome 3) Degenerative Myelopathy (SOD1A) (Chromosome 31) Fetal-Onset Neonatal Neuroaxonal Dystrophy (MFN2) (Chromosome 2) Hypomyelination and Tremors (FNIP2) (Chromosome 15) Shaking Puppy Syndrome, X-linked Generalized Tremor Syndrome (PLP) (Chromosome X) L-2-Hydroxyglutaricaciduria (L2HGDH) (Chromosome 0) Neonatal Encephalopathy with Seizures (NEWS) (ATF2) (Chromosome 36) Polyneuropathy (NDRG1 Exon 15) (Chromosome 13) Polyneuropathy (NDRG1 Exon 4) (Chromosome 13) Narcolepsy (HCRTR2 Intron 6) (Chromosome 12) Progressive Neuronal Abiotrophy (Canine Multiple System Degeneration) (SERAC1 Exon 15) (Chromosome 1) Progressive Neuronal Abiotrophy (Canine Multiple System Degeneration) (SERAC1 Exon 4) (Chromosome 1) Juvenile Laryngeal Paralysis and Polyneuropathy (RAB3GAP1) (Chromosome 19) Hereditary Sensory Autonomic Neuropathy (HSAN), Acral Mutilation Syndrome (GDNF-AS) (Chromosome 4) Juvenile-Onset Polyneuropathy, Leonberger Polyneuropathy 1 (LPN1, ARHGEF10) (Chromosome 16) Dilated Cardiomyopathy (PDK4) (Chromosome 14) Long QT Syndrome (KCNQ1) (Chromosome 18) Muscular Dystrophy Muscular Dystrophy (DMD Cavalier King Charles Spaniel Variant) (Chromosome X) Muscular Dystrophy Muscular Dystrophy (DMD Pembroke Welsh Corgi Variant ) (Chromosome X) Muscular Dystrophy Muscular Dystrophy (DMD Golden Retriever Variant) (Chromosome X)

16 Centronuclear Myopathy (PTPLA) (Chromosome 2) Exercise-Induced Collapse (DNM1) (Chromosome 9) Inherited Myopathy of Great Danes (BIN1) (Chromosome 19) Myotonia Congenita (CLCN1 Exon 7) (Chromosome 16) Myotonia Congenita (CLCN1 Exon 23) (Chromosome 16) Myotubular Myopathy 1, X-linked Myotubular Myopathy (MTM1) (Chromosome X) Hypocatalasia, Acatalasemia (CAT) (Chromosome 18) Pyruvate Dehydrogenase Deficiency (PDP1) (Chromosome 29) Malignant Hyperthermia (RYR1) (Chromosome 1) Imerslund-Grasbeck Syndrome, Selective Cobalamin Malabsorption (CUBN Exon 53) (Chromosome 2) Imerslund-Grasbeck Syndrome, Selective Cobalamin Malabsorption (CUBN Exon 8) (Chromosome 2) Congenital Myasthenic Syndrome (CHAT) (Chromosome 28) Congenital Myasthenic Syndrome (COLQ) (Chromosome 23) Episodic Falling Syndrome (BCAN) (Chromosome 7) Dystrophic Epidermolysis Bullosa (COL7A1) (Chromosome 20) Ectodermal Dysplasia, Skin Fragility Syndrome (PKP1) (Chromosome 7) Ichthyosis, Epidermolytic Hyperkeratosis (KRT10) (Chromosome 9) Ichthyosis (PNPLA1) (Chromosome 12) Ichthyosis (SLC27A4) (Chromosome 9) Focal Non-Epidermolytic Palmoplantar Keratoderma, Pachyonychia Congenita (KRT16) (Chromosome 9) Hereditary Footpad Hyperkeratosis (FAM83G) (Chromosome 5) Hereditary Nasal Parakeratosis (SUV39H2) (Chromosome 2) Musladin-Lueke Syndrome (ADAMTSL2) (Chromosome 9) Cleft Lip and/or Cleft Palate (ADAMTS20) (Chromosome 27) Hereditary Vitamin D-Resistant Rickets (VDR) (Chromosome 27) Oculoskeletal Dysplasia 1, Dwarfism-Retinal Dysplasia 1 (COL9A3) (Chromosome 24) Osteogenesis Imperfecta, Brittle Bone Disease (COL1A2) (Chromosome 14) Osteogenesis Imperfecta, Brittle Bone Disease (SERPINH1) (Chromosome 21) Osteogenesis Imperfecta, Brittle Bone Disease (COL1A1) (Chromosome 9) Osteochondrodysplasia, Skeletal Dwarfism (SLC13A1) (Chromosome 14) Skeletal Dysplasia 2 (COL11A2) (Chromosome 12) Craniomandibular Osteopathy (CMO) (SLC7A2) (Chromosome 5) Information about Embark Embark Veterinary is a canine consumer genetics company offering research-grade genetic tests to owners and breeders. Embark is a research partner of the Cornell University College of Veterinary Medicine and collaborates with scientists and registries to accelerate genetic research in canine health. The Embark test is the only comprehensive test on the market, providing results for over 160 genetic health conditions and accurate breed identification based on over 200,000 genetic markers. We strive to make it easy for customers and vets to understand, share and use their dog s unique genetic profile to improve their pet s health and happiness. You can learn more on our website