Hereditary Considerations

When an animal is born, it receives half of its genetic blueprint from its father and half from its mother. DNA is a fabulous device for conserving everything that makes a living being what it is. Genes represent a region of DNA that influence a particular phene, trait or characteristic. A gene is that portion of DNA that codes for a specific sequence of amino acids, which in turn make proteins, enzymes, or polypeptides. Genetic diseases usually cause problems because a mutation creates a poorly functioning facsimile of the normal gene product. Microsatellites are one way to identify an individual, as well as its progeny, and have become a voluntary part of the DNA identification for the different purebred registries. Genomics is the study of the entire genome, and its combined influence on complex diseases and the impact of environmental factors such as diet, exercise, medications, and toxins on genes. Most traits have polygenic inheritance, in which disease manifestations are controlled by a variety of genes, often with environmental influence. The deeper one delves into genetics and statistics, the more one realizes that, for most conditions, hard statistics do not apply unless a direct test for the genotype exists, and the condition is fully penetrant and expressed. Modifiers, incomplete penetrance, epigenetics, and variable expressivity may have a significant effect on phenotypic outcome. Because accurately predicting genotypes with polygenic traits is difficult and because the environment can have a profound influence, genetic involvement in a trait is typically expressed as heritability, which is a mathematical representation of the variance in breeding values divided by phenotypic variance. Mitochondria contain their own distinct genes, and genetic diseases caused by mitochondrial DNA variants are transmitted from mothers to both male and female offspring. Genes do not cause diseases. They code for proteins that may have developmental or maintenance roles. When those proteins fail to function in a manner consistent with “normal,” an animal may be diagnosed with a phene, trait, or disease of a genetic nature. Still, the relationship between genetics and disease is not as clear cut as one might expect. Fucosidosis is a rare but devastating lysosomal storage disease of English springer spaniels, transmitted as an autosomal recessive trait, meaning a dog would have to inherit an abnormal gene from each parent to be affected by the disease. Epistasis is when the action of one gene depends on the action of another gene. Epistasis is wonderfully illustrated by the coat colors possible with different combinations of alleles from different loci. Oncogenes are genes that when mutated, or expressed at high levels, cause normal cells to transition into cancer cells. Pet-specific care is all about managing risks. All animals have certain risks that pertain to their individual circumstances. For most pets, family history or breed predisposition is a significant contributor to disease susceptibility. Exposure risks constitute another significant contributor to disease susceptibility. Genotypic tests assess a genetic mutation or marker to determine disease susceptibility. Phenotypic tests are those that measure a detectable abnormality or variance from normal, rather than a genetic variant. Collecting relevant information from pet owners is critical to being able to provide truly personalized care for pets. Checklists can be used for more basic functions, such as history taking, presurgical and postsurgical checks, and even to ensure that certain topics are addressed in client educations. Understanding predispositions and risk profiles for individual pets allows veterinarians to create a lifetime care plan for most of their clients, based on the specific risks of each individual patient. In many countries around the world, breeds of pet animals, notably dogs, cats, and rabbits, are becoming more and more extreme in their body shapes. Examples of such extremes could be short legs, long backs, very long ears, excessive hair or hairlessness, pronounced skinfolds, bulging or sunken eyes and, perhaps the most well-recognized, the brachycephalic or flat-faced animals. The veterinary team can make a big difference both throughout the animal's life but also by being involved right from the point of prepurchase decision making. The emotional and financial consequences for the owners can be huge but the whole veterinary team can be affected. Social media can be great for practices, but it is also a powerful tool in getting messages across both consciously and subliminally. Extreme conformation is unnatural and can lead to a variety of health issues and suffering, some of which can be life-threatening. Genetic testing encompasses all evaluations that reveal hereditary predisposition to traits and disorders. These include physical genetic screening for disease as well as DNA tests of the genotype. The majority of genetic diseases and the most commonly seen diseases are complexly inherited and currently have no mutation-based DNA tests available. Some tests measure the phenotype, or what can be seen in the animal. Most tests of the phenotype only identify affected individuals from nonaffected individuals, and not carriers of disease liability genes. Direct mutation-based tests evaluate for specific disease-causing gene mutations. Several breed organizations and/or genetic testing companies list recommended breed-specific genetic tests and screening. The quantity and commercial availability of DNA-based genetic tests are rapidly increasing. Several commercial genetic testing laboratories offer breed-specific “panels” of DNA tests versus running individual tests. Several companies offer DNA testing to identify breed heritage for pets. Genetic health registries compile health data, making that information available to breeders who can then breed with intentionality, owners who can better predict the health of their individual pet, and researchers who can use that information to study disease inheritance and prevalence, and identify emerging health conditions. Many veterinary organizations consider health testing an essential component of veterinary medicine. In their simplest form, genetic health registries are repositories of the results obtained from either phenotypic or genetic health screening test. In general, research into the inheritance and genetic basis of health conditions occurs within university laboratories, institutes, veterinary organizations, and commercial genetic testing enterprises. Veterinarians and owners should explore the information in health registries and use that knowledge in selecting pets to promote overall pet health. Health registries form the backbone of research, which enables the development of genetic tests to reduce disease. The hospital team should be knowledgeable about the genetic tests available, their proper use and interpretation, breed-specific hereditary predispositions, and proper genetic counseling for both owners and breeders of dogs and cats. The predisposition to genetic diseases is lifelong. Consequently, these must be treated as chronic diseases and not just requiring intermittent treatment during clinical episodes. Health-conscious breeders are happy to provide official documentation of the results of health screening. Veterinarians and the veterinary team should be knowledgeable about which genetic disorders have appropriate testing available, and in what patients they should be run. Prebreeding health evaluations should be performed on all prospective breeding cats or dogs, whether for purebred or mixed-breed planned matings. Genetic testing companies are increasingly providing genetic diversity measurements to breeders for individual dogs or cats and their proposed matings. Genetic tests are extremely useful tools to help manage genetic disorders. Veterinary teams need to be prepared for a variety of patients these days, with different breed names, descriptions, and predispositions to disease. In most veterinary practices, approximately half of all canine patients are mixed-breeds, and there are approximately an equal number of purebreds or hybrids. If the information available in practice management software is to be useful for pet-specific strategies, then it is critical that this information be correct in the medical record. Purebred pets are those with a documented pedigree and there are literally hundreds of dog breeds and dozens of cat breeds in the world today. Hybrids are becoming more common in society, as breeders and pet owners attempt to select for specific features by crossing a variety of purebred breeds. Mixed-breed pets have always posed a problem to disease risk prediction, since without knowing breeds, it can be difficult to predict breed predisposition to disease. Many clients acquire a pet without a good understanding of its long-term healthcare needs. This lack of understanding translates both to poor compliance/adherence and to improper planning for a lifetime of healthcare. Most veterinary teams play little or no role in the acquisition of a pet, so clients often begin and complete this process without appropriate healthcare advice. Veterinarians could even provide adoption questionnaires that inquire about health issues in the animals or their parents, and genetic testing that might have been done to mitigate healthcare risks. Helping prospective pet owners understand the ramifications of pet ownership before they actually take on the responsibility of pet ownership is in everyone's best interest. Most selection counseling can be performed by the nonveterinary team and it can be a great bonding experience even without veterinary involvement. To accomplish early detection, both genotypic and phenotypic tests are needed. Genotypic tests examine an individual's DNA for mutations or markers that may be correlated with traits and disease risk. Phenotypic tests measure observable features and diagnostic judgments are made on that basis, and comparisons with so-called “normal” reference intervals. Genotypic tests are available primarily for conditions transmitted as simple Mendelian traits, mostly controlled by one set of genes. Genotypic tests, those that rely on the detection of actual genetic mutations or markers, have a lot of benefits. The best use of genotypic tests is as a health screen rather than a disease screen. Phenotypic tests are more commonly done in practice, including blood tests, urinalysis, imaging, and electrocardiography. Veterinary teams need to be able to effectively counsel clients as how a combination of genotypic and phenotypic testing can help deliver excellent healthcare across a pet's lifespan. From congenital and early-onset conditions, such as angular limb deformities, luxating patella, and hip dysplasia, to developmental conditions that show up later in life, like degenerative joint disease and osteoarthritis, orthopedic conditions can cause significant pain, dysfunction, and secondary complications in canine and feline patients. Orthopedic conditions in cats and dogs can be more common than many people realize and they can often have a significant negative impact on the comfort and quality of life (QOL) of affected animals. Earlier detection and intervention can help improve the QOL for affected pets and their people. While radiographs are a central modality of orthopedic disease screening, they aren't the only diagnostic testing method to use when looking for orthopedic problems in patients. Several suggestions for incorporating orthopedic screening into exams and practice workflows are mentioned. Different breeds have different predispositions to disease states caused by genetic variants. Any personalized care plan should incorporate screening, treatment plans, and client education based on susceptibility to genetic diseases. Disorders caused by a single genetic defect can usually be more easily diagnosed and treated, and more and more genetic (DNA) tests are becoming available all the time. The fact that a pet is not a purebred does not mean that genetic diseases shouldn't be screened for. Diseases caused by recessive genes are less likely to be problems in mixed-breeds but many breeds share susceptibility to the same genetic defects, especially disorders with more complex inheritance that just a single gene mutation. Much of our work in veterinary medicine hinges around the concept of reducing risk. Client education follows risk assessment and management. Breed-specific wellness is the next big leap for educating clients once all the basics have been covered. Patients present with a wide range of ailments. Veterinarians rely upon patient data for clues that explain clinical presentations. Patient data are produced during the comprehensive physical exam and also through diagnostic testing. Reference intervals (RIs) facilitate interpretation of laboratory data because they capture what is considered “normal” for a given species. On complete blood count, Scottish deerhounds have lower than expected RIs for platelets and reticulocytes. Many, but not all, Cavalier King Charles spaniels have moderate thrombocytopenia with larger platelets than is typical. Patients with macro-thrombocytopenia are rarely symptomatic. Elliptocytosis is relatively uncommon in companion animals and is characterized by ovoid erythrocytes. This chapter presents breed-specific hematological and biochemical variations in cats. When the veterinary team keeps current on breed specific clinical pathology, patients are less likely to be misdiagnosed on the basis of values that stray from the norm. Breed-related anesthetic concerns definitely exist in breeds that have a tendency toward anatomical anomalies or development of pathological disease that can impact the safety of anesthesia. Regardless of breed, a good physical exam, history, appropriate diagnostic tests, and a patient-focused anesthetic plan will reduce risk for adverse effects of anesthesia. When the term “breed-related anesthetic adverse events” is mentioned, the brachycephalic breeds (both dogs and cats) are generally at the top of the list of breeds expected to experience these adverse events. Breeds or individuals prone to excitement, anxiety or aggression often need higher dosages of sedatives, and potentially induction drugs, in order to achieve adequate sedation and/or anesthesia. The goal of rational drug therapy is to produce a desired drug effect without causing undue adverse effects. Pharmacogenetics is the study of the genetic determinants of response to drug therapy. Drug absorption, distribution, and elimination can be influenced by polymorphisms, especially in the drug transporter proteins such as P-glycoprotein. The best known breed-related drug sensitivity involves the ABCB1 gene that codes for a P-glycoprotein, a transmembrane protein pump. Intestinal phase I drug metabolism and active drug extrusion by P-glycoprotein transporters are very important in determining oral drug bioavailability. Consequently, genetic variations in these processes dramatically affect oral drug absorption. The P-glycoprotein transporter is an important barrier to the distribution of substrate drugs to protected tissue sites, including the brain, testes, and placenta. Polymorphisms in metabolic pathways may also be involved in idiosyncratic drug reactions. Polymorphisms are genetic mutations that affect drug absorption, distribution, and elimination. The breed should be determined in the initial patient assessment. Different breeds may be at risk for specific diseases or metabolic alterations that require nutritional management. Dogs and cats can be prone to nutritional issues by nature of their size — small breeds vs large breeds. Nutritional recommendations should be based on the individual pet's health and nutritional needs, regardless of breed. Healthcare teams should be familiar with the nutritional feeding goals of large-breed puppies. The primary nutritional considerations implicated in skeletal disease development in growing large-breed/giantbreed dogs are dietary concentrations of protein, energy, and calcium. Proper nutrition has a positive impact on health and disease in all animals. In nutrition for animals, the important point is individualizing the diet for the specific pet, based on the nutritional assessment of that pet. There are many breed inherited disease conditions which can be mitigated or managed with proper nutrition. Many ophthalmic conditions seen in dogs and cats are more frequently observed in certain breeds. While discussing ophthalmic disease, the more common conditions and associated breed predispositions are reviewed. Collie eye anomaly is a recessively inherited ocular disorder seen in a variety of breeds. Primary lens luxation is a condition seen in many breeds where the lens is dislocated from its normal position in the eye caused by abnormal development of the ciliary zonules. This condition can lead to glaucoma, corneal damage, uveitis, and retinal detachments. Genetic testing can further help clients and breeders on improving the breed and helping to reduce or eliminate the disease in future generations. Mixed-breed dogs and cats constitute the majority of pets in most small animal veterinary practices, and there may be misconceptions about their health status compared to purebred animals, as well as their susceptibility to heritable diseases. Hybrid vigor, or heterosis, implies that there are potential health benefits associated with the cross-breeding of different animals. Even in pets that are of mixed heritage, the propagation of heritable diseases is a function of animals with deleterious genetic mutations having the opportunity to contribute offspring to future generations. Genetic testing can provide a lot of information regarding susceptibility to disease. It can be used for screening pets for traits and diseases but in the case of mixed-breed animals, can also be used to infer possible contributing breeds.

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