Steven S. Hannah, PhD
Introduction
Over recent years, tremendous progress has been made in efforts to map and characterize the chromosomes comprising the canine genome. The placement of various types of genetic markers onto a common map has resulted in a useful consolidated canine map. Today the integrated map of the canine genome contains 1800 markers that provide an estimated coverage of over 90% of the genome.1 Feline genetics is also moving forward similar to the canine effort. A genetic linkage map of microsatellites in the domestic cat was published in 1999, constructed using an interspecies backcross pedigree between the domestic cat and the Asian leopard cat and contains over 250 markers with an average intermarker spacing of 11 centi-Morgans. 2
The continued development of high-resolution genetic maps of the dog and cat represent a key resource for identifying genes that control both health and disease. These efforts will result in additional diagnostic tests to identify animals carrying these genes and allow veterinarians, breeders and pet owners to incorporate this knowledge into appropriate health care, nutrition and breeding practices that will minimize the occurrence of genetic disease and maximize the health and longevity of our pets.
More than 300 hereditary diseases have been described in dogs and over 150 hereditary diseases have been reported in domesticated cats. 3-10 Many of these diseases have both genetic and environmental components that together influence the likelihood of an animal developing clinical signs of the disease. In some situations, nutritional strategies can be employed to reduce the risk of the onset of disease. Nutritional management of genetic disease is typically geared toward delivering a nutrient profile that helps reduce the risk of disease in the genetically predisposed animal or in helping to manage the symptoms associated with the active disease process.
Dilated Cardiomyopathy
Taurine has long been recognized as essential for normal retinal function in the domestic cat. Insufficient taurine intake has been shown to result in feline central retinal degeneration.11 Taurine-responsive dilated cardiomyopathy has also been characterized in domestic cats. Dilated cardiomyopathy in the cat has been associated with low plasma taurine concentrations and oral administration of taurine to cats with dilated cardiomyopathy can normalize heart function in many cats. 12
Genetic evaluation of clinical dilated cardiomyopathy in a large cat population suggests that quantitative inheritance is involved in development of the condition.13 The data showed that clinically affected cats were significantly more interrelated than randomly chosen case-control populations from the same colony. Current evidence suggests that, for some cats, prevention of dilated cardiomyopathy requires greater concentrations of taurine in the body than does prevention of feline central retinal degeneration.14-15
Canine Hip Dysplasia and Osteoarthritis
Canine hip dysplasia and subsequent osteoarthritis of the coxofemoral joint remains a major health problem for dog breeders, veterinarians, and owners. While the genetic underpinnings of canine hip dysplasia remain under investigation, nutrition has been found to influence the condition. Restricting the food consumption of growing Labrador retrievers by 25% compared with their control-fed littermates resulted in a marked reduction of the expression of hip dysplasia at 2 years of age.16 Twenty-four littermate pairs were matched according to gender and body weight at 8 weeks of age and fed an identical diet except for the amount of food given each day. Although the limit-fed dogs received 25% less food, meeting the nutritional requirements of the animal was not compromised. At 2 years of age, the incidence of hip dysplasia was 25% in the limit-fed group whereas the incidence was 71% in the control-fed group.
Kealy's group continued feeding the two groups of dogs in this manner and tracked the skeletal health of the animals throughout their lives. Results at 5 years of age indicated that osteoarthritis of the coxofemoral joint occurred at a greater frequency and with more severity in the control-fed group compared to the limit-fed group.17 Based on the results reported in both papers, the authors recommend avoiding overfeeding growing dogs, particularly those breeds prone to hip dysplasia.
Food allergy
Food allergy, or food hypersensitivity, is an immunologically mediated, adverse reaction to an ingested food or food additive. Food allergens are almost exclusively proteins. Most food allergens are highly stable molecules that are resistant to food processing, cooking, and the digestive process.18 A common requisite for any allergen is the ability to stimulate an immune response. The ability to induce an immune-mediated hypersensitivity appears to be dependent upon the size and structure of the protein. The allergens in soy protein, for example, are between 20 and 78 kilo-Daltons.19 If soy protein is enzymatically altered to reduce the molecular weight below this threshold, the resulting modified soy protein should be less likely to elicit an immune-mediated hypersensitivity. Indeed, this is the strategy employed in the development of hydrolyzed protein diets for nutritional management of food allergy in both human and animal nutrition.
Genetic factors appear involved in certain predisposing factors to food allergy. A genetic defect in the suppresser arm of the gut-associated lymphoid tissue (GALT) has been suggested as causative, or at the very least permissive, in hypersensitivities in humans.20-21 The GALT is the component of the immune system responsible for dealing with antigens entering the body through the intestinal tract. The GALT is unique in that it must mount a rapid response to harmful foreign substances while remaining unresponsive to enormous quantities of nutrient antigens. In most food antigen exposures, hypersensitivity is prevented via carefully controlled exposure to the GALT of small quantities of intact proteins. Suppression of local and systemic immune responses to dietary antigens is apparently achieved by involvement of T-suppresser cells, which prevent over-reactivity. If the suppresser system of the GALT is defective, hypersensitivity may occur following exposure to food antigens, which would normally induce oral tolerance.
Nutritional management of food hypersensitivity involves the identification and avoidance of the offending antigenic protein. Classically, this goal has been achieved through the use of proteins considered novel to the animal based on its dietary history. If the animal is genetically predisposed to food hypersensitivity, the immune system may not tolerate the new protein and a hypersensitivity to the new food could develop. The use of enzymatically hydrolyzed protein in diets designed to manage the food allergic dog offers potential advantages over novel-protein diets in that the hydrolyzed protein's antigenicity has been lowered thereby reducing the likelihood that a new hypersensitivity will develop.
Diabetes mellitus
Diabetes mellitus in dogs is characterized by an insulin deficiency or dysfunction that leads to hyperglycemia and abnormalities in lipid and protein metabolism. Diabetes can occur in dogs of any age or sex but is more common in dogs aged 4-14 years of age and is twice as likely to occur in females compared to males. Genetics appears involved in this multifactorial disease. Breeds at higher risk include the Keeshond, Puli, Cairn terrier, Miniature pinscher, and Poodle.22
Dr. Remillard recently reviewed the key nutritional factors for managing diabetic dogs.23 According to her recommendations, dry diets are preferred over soft-moist foods to avoid ingestion of humectants which have been reported to have hyperglycemic effects.24-25 Dry foods appear to have an advantage over canned foods due to a more suitable digestibility coefficient. Diets containing dry-matter digestibility coefficients of 70%-80% are desirable while diets of either extremely high or low digestibility should be avoided unless warranted in dogs that have difficulty maintaining ideal body condition. Dietary fiber helps modulate postprandial blood glucose levels, most likely via delaying gastric emptying, slowing carbohydrate digestion, altering gastrointestinal hormones and producing short-chain fatty acids that may affect hepatic glucose metabolism.26-29 Reducing the intake of fat to below 12% is recommended based on the association of hyperlipidemia with pancreatitis.30-32
Obesity
Obesity is recognized as the most common nutritional problem in dogs and cats.33-36 It is associated with numerous adverse health problems in dogs and cats, such as musculoskeletal problems, compromised immune function, diabetes mellitus, idiopathic hepatic lipidosis and skin problems.37-39
Recent identification of genes associated with obesity in rodents has provided new insight into the genetic basis underlying this condition.40-42 It remains to be seen if similar genes will be found involved with obesity in higher mammalian species such as the dog and cat. A significant breed predisposition to obesity has been shown in dogs indicating a genetic basis as a risk factor.43 Evaluation of the incidence by breed type indicates Cairn terriers, West Highland White terriers, Scottish terriers, Cocker spaniels and Labrador retrievers as high risk for obesity.35
Nutritional management of obesity appears simple in theory: feed less food and the animal will lose weight. But this strategy becomes problematic when determining the amount of caloric restriction to impose to induce safe and effective weight loss. Calculation of a dog's maintenance energy requirements, followed by reduction of intake below this calculated level results in considerable individual variation in weight lost.44 The variation observed when using such a strategy can range from near 0% to 4% body weight lost per week. The development of computer-assisted weight loss programs which make dietary adjustments, based on an individual animal's response to a dietary regime have assisted in tailoring weight loss programs which promote safe and effective weight management.
Summary
In the past, genetics and nutrition were considered two competing forces--nature versus nurture--in modulating the physiology of an individual. Today we know that it is the interaction of genes and nutrients along with other environmental factors that determine phenotype. The interaction of genetics and environment is the foundation for all health and disease. Nutrition represents one of the most modifiable risk factors influencing disease. As with human nutrition guidelines, companion animal nutrition guidelines assume that every animal is at equal disease risk. However, scientific evidence does not support this "one size fits all" approach. Effective strategies to reduce risk of disease will require the identification of individual animals that should be fed diets tailored to their specific dietary needs. Genetic tests are now becoming available to detect the presence of disease genes in dogs and cats.
Reviewed here are some examples of how nutrition can be used to manage genetic disease. Currently, the nutritional strategies are defined by the disease itself, i.e., the nutrient profile of a diet is developed to help manage the symptoms and attempt to normalize the abnormal physiology. As genetic knowledge progresses in the companion animal arena, we will learn more about the genes associated with various health and disease conditions. Identification of these genes will result in advancements in assessing an individual dog or cat's predisposition to disease and other challenges it may face during its life. This knowledge will also enhance our understanding of the physiology underpinning health and disease conditions, which will allow development of more effective nutritional strategies to reduce the risk of expression of genetic disease.
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