An Overview of Feline Diseases & Traits

An Overview of Feline Diseases & Traits Genetic Pet Care The following details provide some general information (educational) on feline diseases symptoms and diagnosis. It is not intended to replace the advice of a veterinarian. If you are concerned that your pet may be displaying any of the described signs or may be prone to one of the diseases described you should see your veterinarian immediately. ORIVET GENETIC PET CARE Suite 102A/163-169 Inkerman Street St Kilda 3182 Australia PO Box 110 St Kilda 3182 VIC Australia t +61 3 9534 1544 f +61 3 9525 3550 Copyright 2014 Orivet > DNA Disease Screening > DNA Traits testing > Canine Breed Identification > DNA Profiling and Parentage Confirmation > Personalised Genetic Health Wellness Plans > Genetic Pet Care Program for Veterinarians > All Natural Pet Care Products > Optimal Breed Selection 3655GRIT

FELINE GENETIC DISEASES POLYCYSTIC KIDNEY DISEASE Breeds: Persian and Related Breeds Polycystic kidney disease (PKD) is an inherited disease that affects the kidneys. It is seen in Persians, Persian-related breeds, and cats with Persian ancestry. PKD is thought to be the most prevalent inherited disease in cats, and various studies and surveys have reported between 36-49% of Persians are affected by PKD. However it is believed that this prevalence is now decreasing due to the availability of a genetic test for the disease and concerted efforts by breeders to reduce the prevalence of the disease amongst their breeding stock. PKD is transmitted as an autosomal dominant trait. This means that an affected cat inherits the disease from only one affected parent. There are no carriers as such; however the disease has variable expression, meaning some cats can be severely affected, while others may have very mild or occasionally even no clinical signs of disease. PKD is diagnosed either by ultrasound of the kidneys to demonstrate cysts, or by a DNA test to detect the presence or absence of the causative PDK1 mutation. The genetic test can be performed on young kittens, but does not give any information about the severity of the disease that they may develop. Ultrasound examination is recommended to be carried out as well as DNA testing, as there are occasionally cases of polycystic kidney disease that are not caused by the PDK1 mutation. HYPERTROPHIC CARDIOMYOPATHY Breeds: Maine Coon, Ragdoll Hypertrophic cardiomyopathy (HCM) is the most common heart condition in cats, with familial (inherited) forms of the disease having been recognised in a number of breeds. The disease in cats is similar to the disease in humans, where more than 120 mutations located on 12 different genes have been shown to be able to cause HCM. Ragdolls, Persians and Maine Coons are amongst breeds with higher than normal rates of disease due to HCM. To date genetic mutations have been characterised in the Ragdoll and Maine Coon and genetic testing is available in these breeds. The mutations are different in the two different breeds, but are both located in the myosin binding protein C gene (MYBPC3). HCM may also occur in these breeds without this particular mutation (i.e. due to a different mutation). The mutations appear to be dominant genes, but with variable penetrance. Diagnosis of HCM is based on a cardiac ultrasound (echocardiogram), and should generally be performed by a specialist. There is no cure for HCM, although if thickening of the heart muscle is secondary to another disease, such as hyperthyroidism, treatment of the primary condition may resolve the cardiac condition. Treatment of HCM aims to manage signs of congestive heart failure, and reduce the abnormality of muscle relaxation as much as possible. SPINAL MUSCULAR ATROPHY Breed: Maine Coon Spinal muscular atrophy (SMA) is an inherited disorder that appears similar to the disease of the same name seen in humans. It is seen in Maine Coon cats, and is inherited as an autosomal recessive disorder, meaning that a copy of the mutation is passed to an affected kitten from both parents. The disease affects the nerve cells in the spinal cord that travel to skeletal muscle of the body (trunk) and legs. These nerve bodies are lost in the first few months of life, leading to weakness and wasting of the muscles of the body. Signs are generally first seen at 15-17 weeks of age, and initial signs include weakness in the hind legs and a very fine tremor in the muscles. Kittens will tire easily and will develop an odd gait, with a swaying in the hindquarters. By 5 months of age they are generally too weak to jump, and examination reveals that muscles of the limbs and body are reduced in size.

PROGRESSIVE RETINAL ATROPHY Breeds: Abyssinian, Somali, Oriental Shorthair, Siamese, Cornish rex, Bengal and Ocicatand related Breeds Tests for both mutations CEP290 (rdac) and CRX (rdy). Progressive retinal atrophy (PRA) is a group of conditions that affect the retina of the eye. The retina is located at the back of the eye, and contains rods and cones, which are specialised cells that are essential for vision. All of the different forms of PRA have the same outcome - the retinal tissue gradually degenerates, leading to a progressive loss of vision. PRA is often classified by the age at which it causes vision loss, e.g. early or late onset The Abyssinian is prone to two forms of PRA. The most common form is an autosomal recessive form called rod-cone degeneration (designated rdac-pra). This is a late onset form of PRA. Degeneration of retinal cells can be detected with an ERG from around 7 months of age, and clinical signs are first detected at around 1.5 to 2 years of age. Blindness is usually complete by the age of 3 to 5 years. The Aby may also be affected by an early onset form of PRA called rod-cone dysplasia (Rdy-PRA), although this is rare. This form of PRA is dominantly inherited and occurs early in life. It can be detected on retinal examination at 8-12 weeks of age. Cats affected with this form of PRA are generally totally blind within a few months of birth. PYRUVATE KINASE DEFICIENCY Breeds: Abyssinian, Bengal, Domestic Shorthair and Longhair, Maine Coon, Norwegian Forest, Siberian, Singapura and Somali Pyruvate Kinase (PK) is an enzyme in the red blood cells that is needed for the production of energy within the cell. When there is a deficiency of this enzyme, the red blood cells cannot produce the energy they need to survive, and an affected cat will be prone to anaemia (a lack of red blood cells in the blood). Red blood cells are the oxygen carrying cells in the blood. There is a genetic test available that can detect affected and carrier cats. There is no cure for PK deficiency. Pyruvate kinase (PK) deficiency is a recessively inherited disease, seen in Abyssinian and Somali cats, as well as domestic shorthairs. The anaemia it causes is often intermittent, so is not always detected on a one-off red cell count (a type of basic blood test). Generally an affected cat will suffer a mild anaemia, or a gradually developing anaemia that she will have time to adapt to, and so may not show any signs of disease. In these cases, although the condition is present from birth, it may not be diagnosed until the cat is quite old. FAMILIAL EPISODIC HYPOKALAEMIA POLYMYOPATHY - BURMESE HYPOKALAEMIA Breed: Burmese This condition is a recessive condition for which the genetic mutation has been characterised and for which a genetic test is now available. Two copies of the mutation are required to cause disease, and the genetic test will determine if a cat is affected (has 2 copies), is a carrier (has 1 copy) or is clear (has no copies) of the causative mutation. This condition occurs in Burmese cats and outcrosses such as the Burmilla, Cornish and Devon Rex, and Tonkinese. This condition generally shows up in young cats (most commonly at puberty, or 3-6 months) but it can also be seen in adults. Low blood levels of K+ may not necessarily be seen at the same time as the muscle weakness, but repeated blood tests will show hypokalaemia over time. Creatine phosphokinase (CPK) is an enzyme that is elevated in the blood as an indicator of muscle damage. This enzyme is commonly elevated in the blood of affected cats. These findings (of low plasma K+ and high CPK) in a Burmese cat showing typical clinical signs helps your vet make the diagnosis of Burmese hypokalaemia.

GANGLIOSIDOSIS - GM2 Breed: Burmese Gangliosidosis (GM2) is a type of lysosomal storage disease, caused by an inherited error in how lipid (fat) is metabolised within cells. Cats with gangliosidosis lack a particular enzyme that is needed to metabolise, or break down certain lipids, and this causes the lipids to build up inside cells because they cannot be excreted. Eventually this interferes with normal processes in the cell, and the cell cannot perform its normal functions anymore. Two types of gangliosidosis are seen in cats, called GM1 gangliosidosis, which is seen in the Korat, Siamese and domestic cat, and GM2 gangliosidosis, seen in the Korat, Burmese, Abyssinian and domestic cat. Gangliosidosis causes a type of lipid (called gangliosidosis) to build up in the cells of the central nervous system (the brain) and leads to neurologic signs in affected cats. Both types are inherited as autosomal recessive, meaning for a cat to be affected she must inherit a defective gene from each of her parents. Cats with only one copy of the affected gene are not affected, but are carriers of the disease. There is no cure for gangliosidosis, but genetic testing is available so that carrier animals may be detected. The only way to manage the disease is prevention by avoiding breeding two carrier animals together. MUCOPOLYSACCHARIDOSIS Breeds: Ragdoll, Siamese and Related Breeds Mucopolysaccharidosis VI (MPS VI) is a type of storage disease and has been noted to affect several breeds of cat, most commonly the Siamese. It has also been seen with a higher than average frequency in the Ragdoll, apparently mainly in those with Australian ancestry. The disease is caused by the lack of an enzyme (arylsulfatase B) that normally breaks down certain cellular products, leading to the incomplete break down of glycosaminoglycan, which then accumulates within certain cells. Two forms of MPS VI have been documented in cats, a mild form, and a severe form. There are two specific genetic tests for the two types, called MPS1 and MPSM (M for the mild form). In addition, a similar disease called Mucopolysaccharidosis VII (MPS VII) occurs in a number of pure breed cats, and there is also a genetic test available for this disease (called the MPS7 test). GLYCOGEN STORAGE DISEASE TYPE IV Breed: Norwegian Forest cat Glycogen storage disease IV (GSD IV) is an autosomal recessive genetic disease, and affected kittens inherit an abnormal copy of the gene that causes the disease from both of their parents. Causes severe (abnormal) levels of glycogen storage in cells. This abnormal level tends to accumulate in muscle and liver leading to progressive organ dysfunction. Both parents carry one copy of this gene, called GBE 1, and are therefore carriers of the disease. The carrier rates in the Norwegian Forest cat populations have been estimated at around 9-12% in Europe and 15% before testing began in the USA. NIEMANN-PICK DISEASE SPHINGOMYELINOSIS Breeds: Siamese, Burmese Niemann-Pick disease (NPD) is a type of lysosomal storage disease. Two types of NPD have been discovered in cats, Niemann-Pick disease type A (NPA) and Niemann-Pick disease type C (NPC).Both are due to the accumulation of certain lipid substances within storage vesicles within the cells of the body. The two types occur due to different genetic mutations, and cause slight differences in the age of onset of disease and the signs that may be seen, however there are many similarities between the two types. The genetic mutation for NPC (on the NPC1 gene) has been characterised in cats. Niemann-Pick disease is seen in the Siamese and domestic cat, and has been documented occasionally in other breeds, such as the Balinese.

FELINE GENETIC TRAITS BLOOD GROUP All breeds Tests for the AB blood group (major blood group) in domestic cats. Types A and B are considered to be the most common with AB considered to the rare group. If a cat is tested as Group A (nonb/nonb) and is dominant to B so therefore is the most common. Type A cats can be AA, Aa or Ab whereas Type B (b/b) will always be bb. The following breeds - Siamese, Burmese, Russian Blue, Ocicat and Oriental Shorthair can only be Type A that is, do not have Type B. Type B is seen more frequently in British Shorhair, Cornish rex and Devon Rex. WHITE GLOVES Breed: Birman Tests for the pattern associated with the white feet pattern associated with the breed. This mutation is fixed in Birman, so all Birmans must have 2 copies of this gene. Autosomal recessive trait 2 copies required to express the phenotype. Also referred to as mittens and is very common in most cat breeds. AGOUTI All breeds Tests for the Agouti Signaling Protein ASIP Results are reported as aa (non agouti) and all aa catsare solid (self) in colour. Tests for solid or banded colouration. Agouti (AA or Aa) also referred to as tabby. Homozygous for the A Locus (AA) the cat will exhibit banded (agouti) hair. If the cat is aa (non-agouti) it will exhibit solid colouration. Agouti is your typical hair colour found in many wild animals. ALBINISM Breeds: Siamese, Burmese Tests for the C Locus associated with the gene. Albino cats are homozygous (cc) for the mutation. The C locus is responsible for white cats with blue eyes. Is associated with deafness. There are some cases where some cats are not completely albino and tend to have one eye pigmented referred to as odd-eyed. There is an association with the W gene and this gene has yet to be identified. AMBER Breed: Norwegian forest cat Tests for the MC1R mutation. If you test as ee (amber) Tests for amber/ red colour to orange. Autosomal recessive mode of inheritance. There are 3 types of genotypes for this mutataion reported as EE (no copy of the Amber gene or Amber colouration is present) Ee one copy of the gene for Amber and ee has2 copies of the gene variant required for amber colour. BROWN/CHOCOLATE/CINNAMON All breeds Testing for lilac the B (tyrosinase-related protein-1, TYRP1) Allele. If a cat tests as bb (has 2 copies of the chocolate gene) then it will be chocolate coat colour. The brown and cinnamon colour is autosomal recessively inherited colour, i.e. the phenotype comes to expression only in cats which inherited these b-alleles from their parents. A cat with genotype b/b has a chocolate-brown colour and a cat of genotype bl/bl has a light brown (cinnamon) colour. A cat with with B/B genotype transmits neither b-allele (for chocolate colour) nor bl -allele (for cinnamon colour) A cat with B/b genotype is a carrier of b-allele b (chocolate), A cat with B/bl -genotype is a carrier of bl -allele (cinnamon ), a cat with b/b-genotype with chocolatebrown colour (homozygous for chocolate allele - this individual always passes this allele on to its offspring). A cat with b/bl -genotype with chocolate-brown colour is a carrier of bl-allele (cinnamon). A cat with bl /bl -genotype with cinnamon colour (homozygous for cinnamon allele - this individual always passes this allele on to its offspring). COLOURED POINTS (POINTS) Breeds: Burmese/Siamese Refers to a cats coat colour associated with a pale body and darker extremities eg. Siamese. Interestingly the gen is carried on the C locus the same gene where albinism is seen together with the same locus as where we see the gene responsible for the sepia pattern. If a cat tests as CC then it is full colour does not carry any Burmese (sepia) or then the cat is Burmese (sepia) Siamese alleles. c s /c s is Siamese. c b/ c bthen the cat is Burmese (sepia). DILUTION All breeds Dilutes black pigment to blue/grey. The gene responsible for colour dilution is referred to as MLPH and is responsible for diluting the black (eumelanin) pigment and is seen in over 25 cat breeds. Black is diluted to grey. Some breeds are fixed for dilute - Cartesian, Russian Blue, Korat and Chartreux these cats are always dd. These cats carry d/d-genotype of D-locus (Dilution).Results are NORMAL DD does not carry blue, CARRIER Dd carries one copy of the blue (does not show the phenotype) and AFFECTED dd colour is diluted. If a cat tests as bb and dd this will result in a lilac colour as seen in British SH/LH. If an orange cats tests as dd then it will be cream, if a chocolate cat bb tests dd then it will be a pale brown. LONG HAIR/SHORT HAIR All breeds Tests for all 4 mutations According to Kehler et al., four mutations in FGF5 gene were identified that cause a cat to have long hair M1(c.356insT), M2 (c.406c>t), M3 (c.474delt) and M4(c.475A>C). Cats that carry two copies of the same mutation (recessive homozygote) or two different mutations of these four mutations (compound heterozygote) have long hair. The mutation M4 was identified in long-haired cats of all breeds involved in the study, the mutations M1, M2 and M3 are specific for some breed types. The M1 mutation was found in Ragdoll breed. The M2 mutation is prevalent in Norwegian Forest cats and the M3 mutation was identified in Ragdoll breed and Maine Coon cats. STATEMENT on FELINE COLOUR TESTING: Please note that feline coat colour cannot be determined by DNA test alone. There are a number of genes that cannot be determined via genetic s and influence colour. These include the O Gene (Orange/Red), the W Gene (dominant White), the Silver Gene and the S Gene (Spotting). To determine the coat colour of a cat the genetic information, pedigree and a photo of the cat tested is required.