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Genotypic tests, those that rely on the detection of actual genetic mutations (variants) or markers (Table 3.11.1), have a lot of benefits. They can be detected at an early age, even as early as one day of age. They don't change over time, so if a genetic mutation is present (or not present) when tested, repeat testing is not needed – the results should not change over time. In fact, if the parents have been tested for a specific variant, the status of the offspring can be inferred from such testing. So, if two Labrador retrievers are both “clear” for progressive rod‐cone degeneration (prcd) and they are bred together, theoretically it should not be possible for the pups to develop that specific form of progressive retinal atrophy (PRA) if the testing has been done by a reliable genetic testing facility (http://bit.ly/2YWXBsc or https://dogwellnet.com/ctp). Of course, mistakes do happen. In this instance, the most likely cause for pups testing “affected” for prcd when the parents tested “clear” would be that the breeders made a mistake in identifying which animals were the actual parents. Theoretically, it would also be possible that the pups developed a spontaneous mutation, but this is very rare.

Table 3.11.1 Some of the genotypic tests currently available

2,8‐Dihydroxyadenine Urolithiasis Type IA

Achromatopsia

Acral Mutilation Syndrome

Acute Respiratory Distress Syndrome

Aggression (markers)

Alanine Aminotransferase (ALT) Activity

Alexander Disease

Amelogenesis Imperfecta

Arrhythmogenic Right Ventricular Cardiomyopathy

Autoimmune lymphoproliferative Syndrome

Bardet–Biedl Syndrome

Bernard Soulier Syndrome

Brain Hypomyelination

Burmese Head Defect

Canine Leukocyte Adhesion Deficiency Types I & III

Canine Multifocal Retinopathy (CMR 1, 2 & 3)

Canine Multiple System Degeneration

Cardiomyopathy, Dilated (DCM1 and DCM2)

Cardiomyopathy, Hypertrophic

Catalase Deficiency

Centronuclear Myopathy

Cerebellar Ataxia

Cerebellar Cortical Degeneration

Cerebellar Hypoplasia

Cerobellar Abiotrophy

Chondrodysplasia

Chondrodystrophy and intervertebral Disc Disease

Ciliary Dyskinesia

Cleft Lip with Syndactyly

Cleft Lip/Palate

Cobalamin Malabsorption

Collie Eye Anomaly/Choroidal Hypoplasia

Color Dilution Alopecia

Complement 3 (C3) deficiency

Cone Degeneration

Cone‐Rod Dystrophy (1, 2, 3, 4, SWD)

Congenital Hypothyroidism with Goiter

Congenital Keratoconjunctivities Sicca and Ichthyosiform Dermatosis

Congenital Macrothrombocytopenia

Congenital Myasthenic Syndrome

Congenital Stationary Night Blindness

Copper Toxicosis

Craniomandibular Osteopathy

Curly Coat Dry Eye Syndrome

Cyclic Hematopoiesis

Cyclic Neutropenia

Cystic renal Dysplasia and Hepatic Fibrosis

Cystinuria (Types I‐A, II‐A, II‐B)

Dandy–Walker Malformation

Day Blindess

Deafness and Vestibular Syndrome

Degenerative Myelopathy

Dental Hypomineralization

Dermatomyositis

Dystrophic Epidermolysis Bullosa

Early Adult Onset Deafness

Early Onset Progressive Polyneuropathy

Ectodermal Dysplasia

Elliptocytosis

Encephalopathy

Epidermolysis Bullosa Simplex

Epidermolytic Hyperkeratosis

Epilepsy (variants)

Episodic Falling Syndrome

Exercise‐Induced Collapse

Exercise‐Induced Metabolic Myopathy

Factor IX Deficiency (Hemophilia B)

Factor VII Deficiency

Factor VIII Deficiency (Hemophilia A)

Factor XI Deficiency

Factor XII Deficiency

Familial Congenital Methemoglobinemia

Familial Juvenile Epilepsy

Familial Nephropathy

Fanconi Syndrome

Fucosidosis

Gall Bladder Mucocele Formation

Gangliosidosis (GM1 & GM2)

Generalized Myoclonic Epilepsy

Glanzmann's Thrombasthenia

Glaucoma

Globoid Cell Leukodystrophy/Krabbe’s Disease

Glomerulopathy KIRREL2

Glycogen Storage Disease IA, II, III, IIIA

Goniodysgenesis and Glaucoma

Hereditary Ataxia

Hereditary Cataracts

Hereditary Deafness (PTPRQ)

Hereditary Footpad Hyperkeratosis

Hereditary Nasal Parakeratosis

Hereditary Nephropathy

Hereditary Nephropathy (Alport Syndrome)

Hip Dysplasia (markers)

Histiocytic Sarcoma (marker)

Hyperekplexia (Startle Disease)

Hyperoxaluria

Hyperuricosuria

Hypoadrenocorticism

Hypocatalasia

Hypokalemic Polymyopathy

Hypomyelination and Tremors

Ichthyosis

Inflammatory Myopathy

Inherited Myopathy

Iron‐Deficiency Anemia

Juvenile Encephalopathy

Juvenile Epilepsy

Juvenile Laryngeal Paralysis and Polyneuropathy

Juvenile Myoclonic Epilepsy

Juvenile Onset Polyneuropathy

L2‐ Hydroxyglutaric Aciduria

Lagotto Storage Disease

Laryngeal Paralysis

Lethal Acrodermatitis MKLN1

Leukoencephalomyelopathy

Ligneous Membranitis

Lipoprotein Lipase Deficiency

Long QT Syndrome

Lundehund Syndrome

Lupoid Dermatosis

Macrothrombocytopenia

Macular Corneal Dystrophy

Malignant Hyperthermia

Mannosidosis

May–Hegglin Anomaly

Microphthalmia, Anophthalmia, and Coloboma

Mucolipidosis II

Mucopolysaccharidosis (I, IIIa, VI, VII, VIII)

Mullerian Duct Syndrome

Multidrug Resistance 1

Multiple System Degeneration

Muscular Dystrophy

Musladin–Lueke Syndrome

Mycobacterium Avium Susceptibility

Myeloperoxidase deficiency

Myostatin Deficiency

Myotonia Congenita

Myotonia Hereditaria

Myotubular Myopathy

Narcolepsy

Necrotizing Meningoencephalitis

Nemaline Myopathy

Neonatal Ataxia

Neonatal Cerebellar Cortical Degeneration

Neonatal Encephalopathy

Neonatal Encephalopathy with Seizures

Neonatal Neuroaxonal Dystrophy

Neuroaxonal Dystrophy

Neurodegenerative Vacuolar Storage Disease

Neuronal Ceroid Lipofuscinosis 1, 2, 4a, 5, 6, 7, 8, 10, A, MFSD8

Niemann‐Pick C

Oculoskeletal Dysplasia

Osteochondrodysplasia

Osteochondromatosis

Osteogenesis Imperfecta

P2Y12 Receptor Platelet Disorder

Palmoplantar Keratoderma

Pancreatitis (marker)

Pannus (marker)

Paroxysmal Dyskinesia

Periodic Fever Syndrome

Persistent Mullerian Duct Syndrome

Phosphofructokinase Deficiency

Pituitary Dwarfism

Platelet Dysfunction

Platelet Procoagulant Deficiency – Scott Syndrome

Polycystic Kidney Disease

Polyneuropathy

Pompe Disease

Porphyria

Postoperative Hemorrhage

Prekallikrein Deficiency

Primary Ciliary Dyskinesia

Primary Lens Luxation

Primary Open Angle Glaucoma

Progress Retinal Atrophy ‐ crd4/cord1

Progressive Neuronal Abiotrophy

Progressive Retinal Atrophy ‐ AD/RHO

Progressive Retinal Atrophy ‐ CNGA

Progressive Retinal Atrophy ‐ CNGB1

Progressive Retinal Atrophy ‐ crd (1, 2, 3, 4)

Progressive Retinal Atrophy ‐ erd

Progressive Retinal Atrophy ‐ Golden Retriever (1 & 2)

Progressive Retinal Atrophy ‐ IG‐PRA1

Progressive Retinal Atrophy ‐ Late Onset

Progressive Retinal Atrophy ‐ rcd (1, 1a, 2, 3, 4)

Progressive Retinal Atrophy ‐ RdAc

Progressive Retinal Atrophy ‐ Rdy

Progressive Retinal Atrophy ‐ SAG

Progressive Retinal Atrophy ‐ Type 1, 3, 4

Progressive Retinal Atrophy ‐ Type A, B

Progressive Retinal Atrophy ‐ Type III

Progressive Retinal Atrophy ‐ X‐linked

Progressive Rod Cone Degeneration (prcd)

Protein‐Losing Nephropathy

Pyruvate Dehydrogenase Phosphatase Deficiency

Pyruvate Kinase Deficiency

Raine Syndrome Dental Hypomineralization

Renal Cystadenocarcinoma and Nodular Dermatofibrosis

Renal Dysplasia

Retinal Degeneration

Rickets

Rod‐Cone Dysplasia 1, 1a, 3

Sanfilippo Syndrome Type A / Mucopolysaccharidosis IIIA (Dachshund Type)

Scott Syndrome

Sensory Ataxic Neuropathy

Sensory Neuropathy

Severe Combined Immunodeficiency (Autosomal)

Severe Combined Immunodeficiency (X‐linked)

Shaking Puppy

Shar‐Pei Inflammatory Disease

Short Tail (Brachyury)

Skeletal Dysplasia

Spinal Dysraphism

Spinal Muscular Atrophy

Spinocerebellar Ataxia

Spondylocostal Dysostosis

Spongiform Leukoencephalomyelopathy

Spongy Degeneration with Cerebellar Ataxia (1 & 2)

Stargardt Disease

Startle Disease

Subacute Necrotizing Encephalopathy

Thrombopathia

Trapped Neutrophil Syndrome

van den Ende‐Gupta Syndrome

von Willebrand Disease Types I, II, and III

Xanthuria Type 1a, 2a, 2b

X‐Linked Ectodermal Dysplasia

X‐Linked Generalized Tremor Syndrome

X‐Linked Hereditary Nephropathy

X‐Linked Myotubular Myopathy

The other big problem with relying on genotypic testing alone is that, at the present time at least, genetic testing is only available for a relatively small number of phenes (conditions, traits, etc.), representing perhaps 20–30% of heritable conditions. Some of the most common conditions with a heritable component, such as allergies or hip dysplasia, have more complex inheritance, often influenced by environmental factors. Such tests that get developed will likely not be entirely predictive, but may indicate whether risk is higher, lower or moderate for an individual, compared to the relevant population base.

Because the body has so many redundancies built into the system, it is also possible that an individual might have a genotypically determined risk but never develop phenotypic disease. It is also possible that a pet has a genotypically determined risk but the phenotypic presentation does not really compromise the animal's health. For example, a Labrador retriever might have a determined risk for exercise‐induced collapse (EIC) but in its typical environment and with its typical exercise regimen, it never becomes problematic.

For some conditions, even though they may be predicted with a genotypic test, phenotypic tests are needed to determine when the condition becomes clinically relevant and treatment is needed, and then for monitoring. For example, the risk for some forms of glaucoma can be predicted based on genotypic testing, but it is still necessary to use intraocular pressure to diagnose clinical disease and as a way of monitoring treatment.

The best use of genotypic tests is as a health screen rather than a disease screen. Pets are typically first examined around 8 weeks of age, and during this period the veterinary healthcare team will search for evident congenital issues, such as malocclusion, umbilical hernia, and luxating patellas. On the basis of this initial physical evaluation, vaccination and parasite control typically begin, and this is also the optimal time for starting pet health insurance, before anything gets identified that would be considered a preexisting condition (see 10.16 Pet Health Insurance).

Then, at 12 weeks of age, genotypic testing is indicated. Since DNA variants and the tests that measure them don't change with age, this can provide a good indication of health, at least for the tests that can be performed at this early age. Similarly, most human infants get postnatal genetic testing, typically for a few dozen hereditary conditions (such as phenylketonuria, congenital hypothyroidism, cystic fibrosis, etc.) – not because the majority of children are expected to have these problems, but it provides peace of mind for the parents that some potential problems can be screened. Postnatal screening does not mean that there won't be any problems that develop later in life, but screening has been done for the things that can be evaluated at this young age.

Phenotypic tests are more commonly done in practice, including blood tests, urinalysis, imaging, electrocardiography, etc. (Table 3.11.2). By 16 weeks of age, phenotypic testing regimens usually begin. This might involve early evaluation for hip dysplasia, urinalysis and tests looking for evidence of “stone” or “crystal formation” in the urine, or even following up on early suspicions of potential congenital heart disease. Further phenotypic testing will likely be predicated on the results of risk assessment (see 2.7 Risk Assessment), but might include definitive screening for hip dysplasia in the mature pet, glaucoma screening based on breed or genetic susceptibility, baseline evaluation of hemograms and biochemistries, and even specialist evaluation of breeding animals by ophthalmologists and/or cardiologists. All of this can be conducted seamlessly within a personalized care plan (see 1.3 Personalized Care Plans).

Of course, phenotypic tests also have their limitations. In some cases, the disease process has to progress considerably before disease will be detected. For example, with diabetes mellitus, a diagnosis might not be confirmed until the patient is clinical and the blood glucose and urine glucose levels rise about a standard point. Prior to that, though, testing may indicate a trend toward that possible outcome. In other cases, such as with prepatent period, a pet may have a parasite, but it is not detectable until it reaches a life stage that is detectable on testing. In other situations, there may not be a single phenotypic test that can render a diagnostic result, so a panel of different tests might be needed to support a diagnosis.

One other feature of some phenotypic tests is that a particular animal (or breed) may not reflect what is considered a “normal range” for the species. For example, there is a DNA test for congenital hypothyroidism with goiter in the toy fox terrier, but no such test for the adult‐onset hypothyroidism more commonly seen in practice. That requires testing with a panel of tests that might include free and total levels of thyroid hormones, thyroid‐stimulating hormone and even autoantibody levels to thyroid hormones. A diagnosis can sometimes still be elusive, especially in breeds that tend not to conform to the reference interval established by the testing laboratory (see 4.8 Pet‐Specific Relevance of Reference Intervals). In these cases, a better approach may be to establish a “normal range” for the individual, by assessing 3–5 tests of thyroid function in the young adult, and using that later in life to evaluate trends.

One important distinction between genotypic and phenotypic testing is that genotypic test results do not change over time and so don't need to be repeated, whereas phenotypic results do change over time so need to be periodically reevaluated. For example, diabetes mellitus is a relatively common chronic disorder in both dogs and cats. In dogs, it is likely a complex genetic disorder in which several susceptibility genes affect overall genetic risk in a breed‐specific manner. Thus, some breeds might be considered at increased risk, including keeshonden, Australian terriers, golden retrievers, miniature schnauzers, pugs, Samoyeds, etc. It cannot currently be predicted with a DNA test, and phenotypic testing with blood glucose levels and urinalysis can either be used to confirm a diagnosis or, preferably, can be used proactively to screen animals at potential risk to identify the prediabetic animal and attempt to alter the course of the disease. To identify such trends regarding the slow progression of such chronic diseases (including glaucoma, hypothyroidism, etc.), veterinary teams need to determine trends by periodically reevaluating relevant phenotypic tests.