In the Mode:
How Traits Pass in Dogs, Lines and Breeds
First printed in Double Helix Network News, Fall 2002
by C.A. Sharp
What dog breeders do is not breeding dogs; normal, healthy dogs can do that without any assistance from us. Breeders manipulate genes, encouraging some to pass on from generation to generation while at the same time trying to prevent others from being so passed. With somewhere around 45 thousand canine genes to work with and, for most of them, no way to know for sure exactly which versions, called alleles, a particular dog carries we are not doing much more than rolling dice unless we develop a thorough understanding of modes of inheritance: How genes flow from a dog to itís offspring, as well as between generations of a line or breed.
Single-gene modes of inheritance
Inheritance from parent to offspring is the most basic and easiest to understand form of gene transmission. Every dog has two copies of each autosomal gene. Autosomal genes are those that are not on the sex chromosomes. One of these copies came from its father and the other from its mother. What combination of alleles it has are its genotype. How they interact with each other, other genes and the environment will determine what traits you will see in the dog, referred to as phenotype.
The most basic mode of inheritance is simple dominance. Black vs. liver color is a classic example. The allele for black is dominant; the allele for liver is recessive. If a dog has at least one copy of the dominant black allele, it will be black. For a dog to be liver, a color produced by the recessive allele, it must have two copies. A black dog might produce liver puppies if it carried a recessive allele, but a liver dog cannot produce black puppies unless bred to a black.
You cannot tell from appearance whether a dog exhibiting a dominant phenotype like black is also carrying a recessive allele. However, knowing the phenotypes of dogs in its pedigree can give you an indication of whether might carry the recessive. If a black dog has a liver parent you know that black dog is heterozygous, meaning it has two different alleles. Such a dog will produce liver if bred to another dog with at least one copy of the liver allele. It has a 50/50 chance of giving a liver allele to each of its pups.
When looking at pedigrees and thinking about autosomal dominant or recessive traits, the breeder should follow the pedigree back step by step along each path of ancestry and note where he first encounters a dog he knows was either heterozygous or homozygous for the recessive. In most cases 4 or 5 generations will be sufficient. The closer up an ancestor with the recessive is, the more likely the recessive allele will have been inherited. Recessive homozygotes always pass the trait but a heterozygous carrier may or may not. If you donít know the genotype of the dominant phenotype individuals that lie between that ancestor and your dog, you canít know for sure if the recessive allele was passed along or not. The farther back the heterozygote is, the less likely the gene will have passed on.
By knowing how many and how far back are the ancestors that you know carried a recessive trait, it is possible to precisely calculate the probability that a dog has inherited the recessive allele. Even the math phobic can have a good idea of what could happen just by studying the pedigree. However there is one factor those who donít want to mess with math need to keep in mind. We tend to think of probability being halved with each generation: Half the genes come from each parent, a quarter from each grandparent, an eighth from each great-grandparent, and so on. This often leads people to the erroneous conclusion that the offspring of two heterozygotes that exhibit the dominant trait all have a 50-50 chance of carrying the recessive gene. This is not the case.
Matings of heterozygotes can produce four allele combinations: Homozygous dominant, homozygous recessive, paternally inherited dominant heterozygote and maternally inherited dominant heterozygote. Three quarters of these are phenotypically dominant. In our black/liver example, that would be three black puppies for every liver. Among the black puppies, two out of three will be carrying the liver allele. Therefore, the odds that any black pup out of such a cross carries liver are not 50/50, but 2 out of 3.
If a recessive trait is something you want, you can use this process to determine how likely you are to be able to produce it in a litter. You can increase the likelihood that it will happen through your mating choices. Conversely, if you do not want to produce the trait you can eliminate the risk of producing it by breeding known or possible carriers to dogs you know are not.
Some genes have an incomplete dominant mode of inheritance. In this case each genotype will have a distinct phenotype, with the heterozygote being intermediate to the dominant and recessive phenotypes. The merle color pattern is an excellent example of this. Dogs with two recessive alleles are not merle, heterozygotes will be merle patterned, and those with two dominant alleles not only have merle patterning but frequently have considerable amounts of white markings and almost always have serious eye defects and deafness. Since the phenotype always indicates the genotype, the breeder will know what alleles the dog has by looking at it.
If alleles are co-dominant, their traits will both be expressed in the heterozygote. The genes in the Major Histocompatibility Complex, which governs important aspects of the immune system are co-dominant. Both maternal and paternal alleles will be active.
Some genes have more than two alleles. Dominance between them may be partial, co-dominant or incomplete. The gene that produces golden/yellow coat color and black masks has a clear dominance hierarchy among itís alleles. The most dominant allele will not produce either, so dogs that have one will have coat color determined by other genes. The most recessive allele, when homozygous, results in hair that is yellowish, as in Golden Retrievers and yellow
If the multiple alleles are incompletely dominant, heterozygotes will be intermediate in phenotype to the two alleles. White markings result from a combination of four alleles which, when homozygous, result in marking variations ranging from no white, to irish pattern, to piebald, to extreme white in that order of dominance. If a dog has one no-white allele and an extreme white, its phenotype will be either irish pattern or piebald.
Not all breeds will have all alleles possible for a particular gene. Knowing which ones your breed has can be important. For years Australian Shepherd breeders have been selecting against extreme white dogs because of their phenotypic similarity to homozygous merles. As a result the most recessive allele for white markings is now extremely rare and may even be purged from the breed gene pool. The piebald allele is still present, though in low frequency for the same reason. It persists because when it is paired with the dominant allele for no white, the dogís phenotype is the acceptable irish pattern. Boxers have a different situation in spite of a breed standard that has similar limits of acceptability for white trim. Boxers have only the most dominant and the most recessive alleles. This affects what breeders must do to avoid producing unacceptable amounts of white. An Aussie breeder can almost always breed two irish pattern dogs and not produce any white puppies. Boxer breeders who do the same thing have a 25% chance of producing them.
There are two other proposed single-gene autosomal modes of inheritance: Dominant with incomplete penetrance and dominant with variable expressivity. With the former, a dog can have the genotype but sometimes will not exhibit the trait. In the latter, how strongly the trait presents can vary considerably. As more and more is learned about how genes interact with each other and the environment, as well as how specific genes are structured and function, it is apparent that neither of these modes of inheritance actually occurs.
They have long been used to describe inheritance patterns that are similar to those described above, but which do not quite meet the statistical standards or which produce phenotypes that are not clearly aligning with the expected genotypes. Traits that have formerly been described as either having incomplete penetrance or expressivity are probably either polygenic or strongly influenced by environmental factors.
Inheritance of genes on the sex chromosomes differs from that of autosomal genes because the sex chromosomes come in two different forms: X and Y. Female mammals have two X chromosomes while males have an X and a Y. The Y chromosome contains only a very few genes, all of them are related to specifically male traits. The X chromosome contains a normal number of genes that produce a wide variety of traits not related to the sex of the individual. However, only one copy of the X can work in any given cell, so females are a "mosaic." Which X operates in each cell is randomly determined during development. This can be most clearly seen in calico cats, in which black and orange are phenotypes produced by different alleles of the same X chromosome gene. Whether a calico cat has a black patch or an orange one at some particular spot on her body will depend on which of her X chromosomes was turned off in an embryologic ancestor of those cells. The exact pattern will have no bearing on what she might produce beyond being an indicator that she has the potential to pass on both black and orange alleles. However, if a particular X allele produces a disease, like hemophilia, it will occur most frequently in male offspring who have only one X. Femalesí mosaicism provides them with sufficient normal cells that they will be healthy. (In the rare case of a female homozygote for hemophilia, she would in most cases die during development. If she did make it to birth she would hemorrhage to death no later then her first heat cycle. )
If a male has an X-linked disease, this is the only time (other than with traits that are clearly autosomal dominant) that a stud owner can truthfully and accurately insist that her stud was not responsible for the problem. These diseases are inherited from mother to son. Each daughter of such a mother has a 50/50 chance of herself being a carrier. The mother of a carrier is probably also a carrier and the health status of her sons should be examined. However, genes for hemophilia and some other X-linked diseases mutate with unusual frequency so one cannot assume that all the bitches on the direct female line were carriers.
Another form of inheritance in which sex plays a role is imprinting. With imprinted genes, the phenotype will be determined by which parent the gene was inherited from. This mode of inheritance is not common and all imprinted genes discovered thus far are involved with development or reproduction.
Unfortunately, most traits are not inherited in a simple, single-gene fashion . Many are polygenic, resulting from the action of multiple genes. At the present time, there is no way to know the genotype of any particular dog for any polygenic trait. The best the breeder can do is make an educated guess. Phenotypes in polygenic traits represent a continuum, rather than a series of similar but more or less distinct types. Canine hip dysplasia (HD) is a prime example. Dogs can have hip joint conformation that ranges from superior to abysmal. Two sound dogs can produce dysplastic offspring and dysplastics can produce sound pups.
With polygenic traits the parental contribution can be unequal. A parent with just one or a few genes that produce the trait may have offspring that exhibit it if mated to a dog that has all the rest. Or the trait may show up after many generations of absence because the right combination of genes finally happened to fall together to produce it. With polygenic traits a breeder must consider the history of the trait in the family, rather than in the pedigree. Dogs that have a family history of the HD (affected siblings, cousins, aunts/uncles or nephews/nieces) are more likely to produce HD than dogs which do not. The more affected relatives there are, the greater the risk.
This kind of family analysis can be useful for producing desired traits as well as avoiding those not wanted. For example, if a dog has an excellent front and comes from a family of excellent fronts, it is less likely to produce incorrect fronts than a similar quality dog that has unusually good front conformation for its family.
Sometimes genes that do not interact with each other produce traits that are nearly always found together. Such genes are linked, occurring close together on the same chromosome. Chromosomal near-neighbors are unlikely to become separated as the genes are shuffled prior to formation of sperm and eggs. If a breeder observes that she cannot find a dog that has a trait she likes without it also having some other thing that she does not like, it may be that the traits are linked. She may have to live with the one if she wants to have the other.
The genetics of the immune system are both polygenic and linked in an extreme degree. The Major Histocompatibility Complex (MHC) is a set of linked genes that are therefore inherited as a unit, called a haplotype. The higher a dogís level of inbreeding and the more recently that inbreeding has occurred, the greater the probability of homozygosity of the MHC haplotypes. This can result in an impaired immune system and reproductive problems. Risk of producing affected offspring is greatly reduced if the breeder makes an effort to produce heterozygous haplotypes by selecting mates that share little or no relationship, especially within the past several generations.
Genes do not act in a vacuum. The environment a dog experiences in the womb and throughout its life impacts the action of its genes. Dogs are born with a certain genetic potential. Whether and how much that inheritance comes to fruition depends on where it lives and what it has experiences, both mentally and physically. This is often described as the "heritability" of a trait.
Heritability is a measure of how much phenotypic variation in a trait results from genes, rather than something else. "Something else" is usually the environment. Hip dysplasia is considered 70% heritable, meaning most of what you see in your dogsí hip joint conformation is the result of genes rather than diet or exercise, the two most important environmental factors. The higher the heritability, the more control the breeder has over the trait.
Some inherited traits, notably chronic autoimmune diseases, require an environmental trigger. The dog must have the genes before it will have the disease, however it is possible that a dog will never develop disease if it never encounters something that triggers the immune system to start attacking the body. Such conditions are said to be genetically predisposed. As with traits of high heritability, the genes must be there in order to produce the trait, no matter what the environmental conditions.
Lines and Breeds
Understanding inheritance in individuals is only the first step a breeder needs to make. Each individual dog is part of a larger population from which its mates will be selected and of which its offspring will become a part. Not every breed will have every allele possible for each gene, as we have seen in the case of Australian Shepherds and Boxers in regard to white markings. MHC haplotypes are another example. Pure breeds have fewer haplotypes than do mongrels, as a group. How few depends on the history of the breed and how much it has been subject to the effects of popular sires and prominent kennels.
Selection criteria need to be sufficiently broad, encompassing not just physical attributes, but health, behavior and temperament. Strong selection for or against a particular trait or a few traits can skew a gene pool and inadvertently result in lowered frequency or eliminating some alleles and at the same time increasing or "fixing" others. (An allele is fixed in a population if it is the only one present.) This may be good or bad, depending on what those alleles happen to do. It is one way that breeders may "suddenly" start producing a particular disease or problem that had rarely been noted before.
Breeding according to the current fashion via selecting for this yearís winning "look," or the excessive use of a popular sire or the output of a prominent kennel can likewise skew a breed gene pool and result in unintended consequences. The smaller the breed population, the greater the effect narrow selection criteria and breeding for fashion will have.
A line is an extended family of dogs. It is developed by some degree of inbreeding and thus will necessarily have only a sub-set of the alleles present in the breed. The composition of this sub-set can be altered through the same things that will alter allele frequency in the breed. Since a line is necessarily a smaller population the effects can be more drastic. Desired traits, particularly those that are easily observed and no much influenced by environment, can be made fairly uniform in a relative few generations. However, unwanted traits may become intractable features: Epilepsy has become just such a problem in show-line Australian Shepherds in little over a decade.
New (or lost) alleles can be brought into a line by the simple expedient of outcrossing. On a breed-wide scale, however, this can be difficult in our current system of closed registries. For breeds with wide geographic distribution, imports may provide sources of fresh genetic material provided the exporting countryís registry is considered acceptable and that the populations are not already substantially related. In a few cases the American Kennel Club has allowed significant additions of fresh stock at the request of member clubs, most notably the admission of a few African tribal Basenjis about 25 years ago and the current acceptance of some individuals of recent desert origin from a small
The breederís task is to effectively utilize what is known about modes of inheritance for breed traits, both positive and negative, in order to produce quality dogs that not only meet his competitive or performance goals but which are also physically and mentally healthy. He must at all times remember that he does not act in isolation. Whatever he does will have an impact on breeders that follow. The greater his success, the greater his impact for good or for ill will be.
Copyright 2002 C. A. Sharp.†† All rights reserved.†† C.A. Sharp is editor of the "Double Helix Network News", the quarterly newsletter for those interested in genetics and hereditary disease in the Australian Shepherd. †