Real World Genetics

A gene is a length of DNA that codes for a particular polypeptide. A polypeptide is a piece of a protein. Polypeptides, and thus proteins, are made up of small molecules called amino acids. Put the right set of amino acids together the right way and you get a protein. Put them together the wrong way and you get, frequently, a nonfunctional or only partially functional protein. The important point is this: Genes code for proteins, not directly for traits. This matters because complicated traits are probably influenced by a lot of different genes (they are polygenic; the genes involved are sometimes called polygenes). Even “simple” traits may not turn out to be all that simple once you really look at them.

In complete dominance, both GG and Gg animals are gray and there is no way to tell what their genotypes just by looking at them. Only gg animals are not gray. If dominance is incomplete, then GG animals would be gray, gg animals would be non-gray, and Gg animals would be intermediate in phenotype. In real life, G appears to be completely dominant to g.

Where incomplete dominance gives us heterozygotes with intermediate phenotype, codominance gives us heterozygotes which express both dominant and recessive traits at the same time. The classic example is seen in human blood types: You can be type A (genotype AA), type B (genotype BB) or type AB (genotype AB). In codominant traits, two different alleles are probably coding for different proteins, both of which are functional, but in different ways. There are probably quite a few codominant traits, but relatively few which are visible in simple phenotypic terms.

In this unhappy situation, one genotype is taken out of the picture because it suffers such severe problems that it dies. Lethals need not be literally all-the-way lethal to have a substantial effect on a breed. In dogs, merle can act as a deleterious dominant, although not actually lethal in most cases: Mm animals show merle coloring where they would otherwise have been black, mm animals are non-merle, and MM animals are frequently blind or deaf or both, as well as mostly white. Some sources indicate that the deleterious effects of the MM genotype seem to be partially or wholly offset if the dog has no other white markings – a MM sheltie is likely to have serious problems, it is said, whereas apparently a MM Dachshund is not. Breeding around lethals requires basic familiarity with genetics.

This simply means that the trait in question is controlled by a gene located on the X chromosome. Since dogs have 39 pairs of chromosomes (compared to the human 23), we would not expect a very large percentage of traits to be located on the X chromosome. If a trait is X-linked and also deleterious, you would expect most of the puppies produced with the trait to be male. This is because the most typical situation would be a normal but carrier dam bred to a normal sire – both parents would be phenotypically normal, but half the sons (on average) would be affected by the trait (and half the daughters would be carriers). If the trait is not significantly deleterious (such as color-blindness in humans), then you would expect affected males to be used in breeding (since no one would care about the trait) and the ratio of affected males and females would probably be closer to even, although even then you would expect more affected males than females.

Genes are said to be “linked” when they are physically located near one another on the same chromosome. Linkage becomes important because linked genes do not sort independently. “Linkage groups” are groups of genes that are all close to one another. Some genetic tests test directly for genes that are responsible for a problem, but others are linkage tests that test for genes linked to the genes that actually cause the problem. Linkage is never absolute; it can be broken by crossing over between homologous pairs of chromosomes when gametes (sperm or eggs) are formed.

Epistasis is a term used to refer to one gene acting “dominant” to a different gene at a different locus. Note that this is not one allele being dominant to another in the same gene series, but one gene altering the effect of another. A good example in dogs is the ee genotype at the extension locus creating a clear red or yellow color regardless of what alleles are present at the agouti locus. Thus Blenheim cavaliers are black-and-tan at the agouti locus, but expression of the black pigment in their coats is suppressed by the red dilute ee. In this case, the agouti locus would also be said to be hypostatic.

When one gene influences more than one trait, it is said to be pleiotropic. Thus the merle dilute in dogs not only turns black areas into a patchwork of black and gray, it also can influence ear and eye development, particularly if homozygous. "Extra" effects need not be deleterious. The cystic fibrosis allele not only causes disease in its homozygous state, but in its heterozygous state also protects against respiratory disease.

When many genes influence one trait, the trait is said to be polygenic. It is typical for polygenic traits, such as temperament and hip dysplasia, to show environmental effects. However, a reasonable rule of thumb is if a trait is both complicated anatomically and affected by environmental factors, it is very likely polygenic. In contrast, if a simple metabolic pathway is easy to visualize for a trait and it does not seem to be affected by environmental factors, it is more likely to be genetically simple – especially if the same or similar traits are known to be simple in other breeds or other species.

Two common models for polygeny are additive polygeny and threshold polygeny.

Additive polygeny would work like this: Suppose that each of nine genes adds a “dose” of pigment when present in the dominant form, but not when recessive. Then an animal with a AABBCcddEEFfGGHHii genotype would have very dark pigment (although not quite as dark as possible), whereas a aabbCcddEEffggHhii animal would have very light pigment (although not as light as possible). When plotted on a graph, the possible genotypes for this trait would yield a bell-shaped (normal) curve, with most of the animals being intermediate and a “tail” out towards the extremes on both sides. You could, as a breeder, select for either extreme, but it would not be nearly as easy to achieve consistent dark pigment in this situation as it would if pigment was controlled by a simple one- or two-gene system. Traits such as pigment modifiers, height, some kinds of coat texture, and intelligence are easy to visualize as additive traits. Eye color in dogs is also thought to work this way.

Threshold polygeny would work like this: suppose that six genes control the development of hip dysplasia, in such a way that at least three of the genes must be homozygous recessive before any degree of dysplasia exists, and after that more recessive alleles mean the dysplasia is likely to be progressively worse. The three-gene requirement would then be the “threshold” that flips a switch and determines whether dysplasia is present at all; the other alleles plus environmental factors then determine how severe the dysplasia will be. You can usually assume, when faced with a polygenic trait, that both parents of an affected animal contributed some deleterious alleles. Their contributions need not, however, have been equal.

Models like this seem to have reasonable predictive power when applied to the way many polygenic traits are inherited in dogs. It's important to assess the siblings of breeding animals in order to make the best guess possible about the genetic quality of the animals you keep to breed, because looking at the whole family makes it easier to assess how many deleterious alleles are likely to be floating around in the family.