Genetics research and use of new technologies leading to tests for genetic related diseases has increased the visibility of this discipline in the dog’s world.
This page aims to inform you not only on genetic disorders but also on multifactorial causes as genetics and environmental factors interacts whenever it concerns physical (as in hip dysplasia) or behavioural traits. Studies are regularly bringing increased knowledge and we shall try to keep you informed of the latest developments.
What is a genetic disorder? (courtesy of University of Prince Edward Island)
Most diseases are affected to some extent by both genes and the environment. A genetic disorder is one in which an abnormality in the genetic make-up (the genome) of the individual plays a significant role in causing the condition. Although some disorders occur because of spontaneous mutation, many genetic disorders are inherited. These conditions are seen quite often in dogs, mostly but not exclusively in pure-breds. These situations are often heart-breaking because the dog is generally a well-loved family member by the time the condition is apparent and has been diagnosed by a veterinarian.
The role of genes in disease
The role played by genes in disease is becoming better understood. Genetic factors are involved to a greater or lesser extent in congenital malformations (conditions with which an animal is born), metabolic disorders, disorders of immune function, disorders associated with ageing, and cancer. These categories of disease have become relatively more important as infectious, parasitic, and nutritional diseases have become less common due to vaccination programmes and advancing knowledge about nutrition, treatments and diagnostic methods.
How to reduce inherited disorders
The frequency of inherited conditions can be reduced through good breeding practices. For this to occur, we need to know how the disease is inherited (the mode of inheritance), how to identify the condition as early as possible, and ways to recognize carriers of the disease who, except in the case of autosomal dominant traits, are not clinically affected.
For many of the disorders that are believed to be inherited, the specific pattern of inheritance has not been established. Breeds that have an increased risk for a condition, relative to other dog breeds, are said to have a breed predisposition. Preferably, affected dogs and their close relatives should not be used in breeding programmes.
Only 1 copy of the gene, which may be inherited from either parent, is required to produce the trait. The parent with the dominant trait will pass the affected gene to approximately half its offspring, and the trait will be apparent in both the parent and the affected progeny. These conditions are uncommon because, as long as it is of early onset (ie becomes apparent before breeding age is reached), the disorder can be readily eliminated by avoiding the breeding of affected individuals.
In many instances however, there is incomplete dominance. The trait may be dominant with variable expressivity, which means that if either parent is affected, all puppies have a susceptibility to the disorder but not all will be affected equally. Alternately, a dominant trait may have incomplete penetrance. If penetrance is 75% for example, only about 3 quarters of the pups who inherit the trait will express it.
This is the most common mode of inheritance for genetic conditions in dogs. Progressive retinal atrophy (PRA), which causes blindness in many breeds, is such a trait. To be affected, the animal must inherit 2 copies of the gene (genotype pp), 1 from each parent. Dogs with the genotype PP (normal) or Pp (carrier) will be clinically normal but the carrier will pass the affected gene to approximately half the offspring. As long as carriers (Pp) are mated to normal animals (PP), the offspring will be unaffected but some will remain carriers. If 2 carriers are mated, some of the offspring (approximately 25%) will be affected.
As long as the frequency of a gene for a recessive disorder remains low in the population, the particular gene may be passed along for many generations before by chance 2 carriers are mated and affected individuals are born. However, the gene frequency may become unusually high due to breeding of close family members, or because of the “popular sire” effect , where a sire with a harmful recessive gene is mated frequently because of desirable traits.
Because the recessive gene is carried in the population in outwardly normal animals, it is very difficult to eradicate these traits. However the incidence can be reduced by identification of carriers through test matings or through various tests that have been developed, and the conscientious use of this information in breeding programmes. Veterinarians, dog breeders, and breed associations must all work together for substantial progress to be achieved.
In these traits, the gene is located on the X chromosome. Males have 1 X chromosome from their mother, and 1 Y chromosome from their father, which carries little information other than maleness. Females have 2 X chromosomes, 1 each from their mother and father. So if a mother who is a carrier for a harmful recessive gene (Xx) passes the recessive gene (x) to her daughter, the daughter will be an unaffected carrier, but her sons who receive that gene will be affected.
The bleeding disorder hemophilia is the best known of the X-linked traits, which are uncommon in the dog. Control programmes are possible because carrier females can be identified through blood screening.
The above-mentioned traits are inherited in a straightforward manner. Many others are inherited in a more complex fashion. In fact, most traits that are selected for in the dog are the result of the interaction of many genes. Modifying genes may influence how other genes are expressed. As mentioned above, a trait may be dominant, but with incomplete penetrance so that it is not always expressed. Epistaxis occurs when alleles at one locus mask the action of another pair of alleles.
Polygenic traits are controlled by an unknown number of genes. The gene expression is influenced by a variety of factors including gender, nutrition, breed, rate of growth, and amount of exercise. These traits are quantitative traits – that is, there is a wide range within the population. Such traits include height, weight, character, working abilities, and some genetic defects. Heritability varies within different breeds and within different populations of a particular breed.
Because it is virtually impossible to determine the exact genotype for such traits, it is difficult to control defects with a polygenic mode of inheritance. The best attempts at control are based on a grading scheme for identification of the defect and a breed policy of recording and publishing the results for as many dogs as possible. Canine hip dysplasia is a polygenic trait that remains a problem in most large breeds of dog, despite efforts to control this condition dating back to the 1960s. Breed organizations and veterinarians in various countries have developed control programmes that rely on radiographic evaluation and a central registry of dogs. Thoughtful selection by breeders, using this information, has greatly reduced the incidence of hip dysplasia in those breeds in particular countries.
Genetic and environmental factors in hip dysplasia
Hip dysplasia is a hot topic in dogs, if it’s possible to stay “hot” for 50 years. Researchers have been working hard for decades looking for solutions, and breeders have been doing their best to reduce the risk of producing affected puppies. But still the problem remains.
There are some simple things we could do to reduce the incidence of hip dysplasia now if we understand a few basic things. Here are the 10 most important things you need to know.
1) All puppies are born with perfectly normal hips
Hip dysplasia is not a congenital defect; it is not present at birth. Multiple studies have demonstrated that all normal puppies are born with “perfect” hips; that is, they are “normal” for a newborn with no signs of dysplasia. The structures of the hip joint are cartilage at birth and only become bone as the puppy grows. If a puppy is going to develop hip dysplasia, the process begins shortly after birth.
This is the hip joint of a 1 day old puppy. The cartilage tissue does not show up on an x-ray until the minerals are deposited that form bone. Proper development of the joint depends on maintaining the proper fit between the head of the femur and the socket (acetabulum).
“The hip joints of all dogs are normal at birth. The joints continue to develop normally as long as full congruity is maintained between the acetabulum and the femoral head… The acetabular rims are stimulated to grow by mild traction applied by the joint capsule and gluteal muscles attached along their dorsal borders, and from pressure by the femoral heads upon the articular surfaces… The morphologic characteristics of the complex hip structure show that biomechanical behavior is the prime influence in the growth of this joint.” (Riser 1985)
2) The genes that cause hip dysplasia remain a mystery
Hip dysplasia tends to be more common in some breeds than others and in some lines than others, which indicates that there is a genetic component to the disorder. However, scientists have been looking for genes that are responsible for the development of hip dysplasia in dogs for decades without success.Genes that are associated with hip dysplasia have been identified in some breeds, but they are breed-specific; that is, the assortment of genes is different in every breed. (For example, see studies on the German Shepherd dog (Marschall & Distl 2007, Fells & Distl 2014, and Fels et al 2014), Bernese Mountain Dog (Pfahler & Distl 2012), and Labrador Retriever (Phavaphutanon et al 2008). Genes that could cause hip dysplasia have not been found in any breed.
It’s unlikely that researchers are going to discover an easy genetic solution to the problem of hip dysplasia. It is a complex trait that is influenced by both genes and environment, and there is no simple solution just over the horizon. We should be able to improve genetic progress by using selection strategies that are as efficient and effective as possible such as estimated breeding values, EBVs. One great advantage of using EBVs is that the genes responsible for a trait don’t need to be known; you need only a pedigree database and information about affected animals.
3) Environmental factors are also important
Although there is a genetic influence on hip dysplasia, the heritability of the trait is rather low. Many studies have shown that genetic variation accounts for only a modest fraction of the variation in hip scores, usually 15-40%. This means that some fraction of the variation in the quality of the hips is the result of non-genetic, or “environmental” influences. This is one reason why decades of strong selection has resulted in only modest reductions in hip dysplasia in some breeds. At the current rate of progress and selecting only by phenotype, it could take decades to achieve a meaningful reduction in the incidence of hip dysplasia (Lewis et al 2013).Understanding the specific environmental factors that play a role in the development of hip dysplasia should allow us to reduce the number of animals affected by hip dysplasia even if the genetic basis is not yet understood. This would reduce significant pain and suffering as well as the expense and heartache endured by owners of an afflicted dog. There is no reason why we should not be taking active steps to do this now.
The top three environmental factors that have been found to play a significant role in the develop of dysplastic hips are: a) joint laxity, b) weight, and c) exercise. Read full article
How genetics and environment influence behaviour
Genetics and epigenetics
Behaviour results from both genetics and environment. In some cases, specific behavioral traits have been mapped to specific gene loci. In other cases, we can observe clear evidence of behavioral traits in certain related lines, but have not identified any specific gene or genes responsible for the traits. The study of heritability provides evidence of the inheritance of various behavioral traits. One way of describing the impact of genes on behavior is to imagine that, given a particular genotype, each trait (e.g., boldness, shyness, curiosity, sociality, predatoriness, etc.) has a potential range of expression. A given animal may be more or less bold, depending on subsequent learning. But it may never be as bold as a littermate whose genes dictate a different, bolder range.
Most DNA is functionally identical from one dog to the next. The dog and wolf genomes show even more similarity than the human and chimpanzee genomes, which are over 99 percent identical. Between dog breeds, or individual dogs, that similarity is even greater. Although dogs show genetic plasticity unrivaled in the animal kingdom, the differences between one dog’s DNA and another dog’s DNA are very tiny. Yet these small differences can produce functionally significant behavioral differences. Dog breeds don’t differ just in appearance; they also differ in behavioral tendencies. We can make some behavioral predictions based on breed, though actual familiarity with a given dog’s close family members will greatly improve predictability. Not all Border collies can do a good job herding sheep, but very few Labradors can do even a lousy job herding sheep. We’ve repeatedly seen that herding breed dogs are more likely to react to movement, terriers are more likely to fixate on squirrels, bulldogs are more likely to fight than flee when faced with social conflict, some gun dogs are more likely to invade dog and human personal space while failing to recognize the body language of discomfort, and so on.
Likewise, traits like boldness, social fearfulness, neophobia, bite style and strength, ease of socialization, sound sensitivity, and certain other traits that are highly pertinent to many of the behavior problems we repeatedly work with have a genetic basis. Some of these can track by breed.. Clarence Pfaffenberger looked at Labrador puppies bred for guide dog work, and concluded that the pups were able become well-adjusted with just one weekly socialization session during their socialization period, which is much less than most professionals recommend. My observations tally with this: Typical Labradors and golden retrievers can become successfully socialized to humans in general by meeting relatively few during the critical socialization period. By contrast, the independent or rural working or herding breeds tend to need much more carefully managed, broad, and systematic socialization to a wide variety of people to achieve the same level of social comfort. (This doesn’t give carte blanche to be sloppy about socializing any dog, but it means the risks from not socializing an Australian shepherd correctly to home life might be much greater than slapdash exposures for a Cavalier King Charles spaniel.)
Phenotypic traits (those actually exhibited by the organism) can result from a single gene; an example of this is the merle gene, causing patches of dilute and non-dilute color on the coat. A single gene, SILV, controls whether merle patterning is or is not present. Most traits are likely influenced by multiple genes working together. Epilepsy in most dog breeds is an example; scientists have failed to locate single genes associated with epilepsy. (A couple of breeds have specific monogenic epilepsy.)
We know relatively little about genes that affect behavior, but as a general matter, it’s likely that most behavioral traits are polygenic—meaning it’s not likely that research will discover one gene “for” aggression, herding, or anxiety, rather there will be a set of genes that all contribute to whether a dog has this trait.
Epigenetics refers to heritable changes in organisms caused by modification of gene expression, rather than alteration of the genetic code itself. Researchers have shown that how a mother rat nurtures her young after birth directly impacts the anxiety levels of her pups even as adults, and that this results partly from her behavior affecting which of the pup’s genes are expressed. It is assumed that epigenetic processes affect development of physical and behavioral traits in dogs, and provide a crucial link between the nature of the genes themselves and the nurture of the environment. For our purposes, the key points about epigenetic processes are that (a) they can cause different outcomes in genetically similar organisms, (b) epigenetic changes to genes can then, themselves, be inherited; and (c) epigenetic changes from stress are well-known to impact future behavior.
A good, basic glossary of numerous genetic terms can be found at www.genome.gov/glossary/. There are both audio and text versions of the glossary.
Once conception has taken place, each puppy in the litter has received an assortment of genes, half from the dam and half from the sire. (It’s not really quite 50/50 in males, because the Y chromosome does not have as many gene loci as the X chromosome.) After conception, puppies have the genes they’re always going to have. As each individual grows and develops into adulthood, each trait matures within a limited range of values. Where in that range the organism ends up depends on environmental influences following conception. Environmental influences range from the uterine environment all the way to learning before maturation is complete. These environmental influences affect whether a child ends up being 175 cm tall or 180 cm tall, as a simple example. Likewise, they can control whether a puppy ends up terrified of the world or merely neophobic and cautious, fun-loving or recklessly sensation-seeking.
Stress on the fetus while it is still in the womb is the first environmental factor that can affect development of a trait. Adverse effects on both physical and behavioral traits have been widely documented in many mammalian species. There is no reason not to assume the same problems will occur in dogs. Uterine stress occurs as a result of environmental impacts on the mother. These could include malnutrition, toxic chemical exposure, unsafe living conditions, social stress, and many other factors that have been documented in numerous species such as mice, foxes, and marmosets, though little work has been done in dogs.
Neonatal stress will also have an effect. The same stressors that can affect puppies indirectly via stress to the dam during pregnancy may affect puppies directly after birth, while nursing dam malnutrition can continue to affect puppy nutrition. Additionally, the dam’s behavior may cause adverse effects on the newborn puppies, particularly if the dam is unskilled or exhibits abnormal behavior toward her puppies.
As the puppies mature and their eyes and ears become fully operational, the channels for perceiving the world and its potential stressors increase. The puppy socialization critical learning period is underway, and learning at this time creates powerful impacts on the pups’ expectations of the world. Unkind treatment by dogs and people may start to teach puppies about who and what is safe or dangerous. Likewise, if the dam is defensive about the presence of people or other dogs, the puppies will learn socially that people or other dogs are dangerous or threatening. There are various models or proposed mechanisms for this kind of learning, for example “stress contagion” and “vicarious learning.” These early impressions will influence the puppies’ attitudes toward key members of their social groups forever.
Once the critical primary socialization period has passed, most of temperament formation is probably done. At this point, it’s hard to change the basic “presets” of stable temperament features. As we—or our clients—care for a dog, we can confirm or fail to confirm what we might call the dog’s biases toward the world and its denizens, but our opportunity to move the settings is limited and smaller every day. In my experience, the major exception to this is in how we respond to new behaviors that may emerge around puberty. (I suspect this is what’s referred to as a “second fear period,” but that’s a topic for another article.) A previously unreactive dog who lets out an adult-sounding bark at an unusual-looking stranger at 8 months may well be showing genetically-rooted fear or defensiveness. Since this is the first time he has exhibited this particular behavior, the handler’s response will constitute 100 percent of the dog’s learning history with respect to it. (Of course, the dog will have already experienced responses to bold, timid, noisy, or quiet behavior, which should affect that learning history somewhat.) This means the handler’s response can affect future behavioral choices powerfully at this age, and handlers and trainers must be aware of this final period of unusual developmental opportunity or risk.
A final tricky aspect of the development of personality in the dog is that, while environmental influences become much less potent after puberty, the expression of personality is still maturing and changing until the dog reaches social adulthood—at about 2 to 3 years of age. (Giant breeds mature later in this range, while small and medium breeds, particularly working, terrier, herding, and primitive/Spitz breeds tend to mature earlier in the range. The common rule of thumb in working with pit bulls—that if gameness (the desire to fight uninhibitedly with other dogs) has not manifested by the age of 3 years, it probably is not going to show up—is an example of this.) Mild cautiousness appearing at 8 months may not seem concerning, but at this age, a dog is just starting to display age-appropriate independence. That caution can develop into suspicion at 12 months and forward threat behaviours at 15 months, taking by surprise an owner still operating under their initial impressions of a social, attached, and charming puppy. Thus, even after the ingredients are all added to the bowl, changes are still occurring like a yeast dough rising, unseen, under a kitchen towel. Because future changes can be invisible at the time they are triggered, it can be difficult to get a handler to take these sensitive periods and mechanisms of change seriously while the puppy is still puppy like.
Read more in the full article