Kindergarten Genetics
Or, just enough to get you started (plus links)
A fair number of people, it seems to me, get interested in dogs, decide to breed, realize (perhaps with a sinking feeling) that they really ought to learn something about genetics so they can do a decent job . . . and don't know quite how to get started. Or can't quite bring themselves to get started. Yuck. Genetics. It's kind of like . . . math.
This prevents people from just jumping in and getting started.
I’ve met my share of folks -- I really have -- who apparently think that “dominant” means “common in the population” and “recessive” means “bad.” Neither idea will be helpful when trying to understand what genetics is all about, much less when thinking about establishing your own breeding program!
Well, I came into breeding backwards: I was teaching basic genetics in courses I TAed as a graduate student before I ever bought my first dog as a pet -- long before it ever occurred to me to show or breed. I got interested in genetics for its own sake, because the coat-color stuff seemed interesting, not because it occurred to me it might be personally useful to me. I'd been studying genetics casually for quite a few years before I decided to buy a good bitch puppy and get into the practical end of things for real. This gave me a step up for which I'm now grateful.
Now I'm in a position to say, sincerely, that learning about genetics can be -- ought to be -- fun. Even if you're mathematically impaired. The genetics underlying coat colors is relatively simple and a good place to start if you decide to dabble, even though I'm sure we all agree that coat color is trivial compared to other traits, like the soundness of the heart or hips.
I'm sure there's a "Genetics for Dummies" book out, and it's probably pretty good -- the "Dummies" books I've looked at have mostly seemed basically solid. I think there's a Cartoon Guide to Genetics, and it's probably just fine for the basics, too. There are a lot of books out aimed at dog breeders that do a good job with introductory genetics, although rather fewer that go on to the really interesting (and actually useful) stuff. Like anything else, just getting primed with the basics won't do much to help you in real life. Unless all you care about really is coat color. And there're lots and lots and lots of web sites, some of which offer really good information and some of which (of course) offer misleading or outright wrong information. Some good links are included below.
My aim here is not to be exhaustive, but just to offer a very brief guide to the absolute basics.
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Eight basic terms you will need to know (plus a few extras I'll sneak in around the edges):
Gene – a unit of DNA that “codes for” a particular trait. More than one gene can influence the same trait and in fact that is usually the case. Traits like that are often referred to as polygenic -- poly for many and genic for gene. They are also called "complex" traits. Some traits are controlled entirely or primarily by just one gene, and those are much easier to deal with in a breeding program. Those are referred to as "simple" or "one-gene" or "monogenic" traits.
Allele – one form of a particular gene. In dogs, for example, the allele G codes for grey color (you see the action of this allele in Kerry Blue, Bedlington, and Dandie Dinmont Terriers) while the allele g codes for normal (non-grey) color. These are alternate forms of the same gene.
Don’t let the little letters bother you. I’ll use the simplest possible letter codes, but it’s not possible to really talk about genetics without using some kind of letter terminology. So: G for grey and g for non-grey. Simple, yes?
It’s common for people to use the word gene when they mean allele. In my opinion this promotes more confusion than it’s worth. For heaven’s sake, it’s only one additional vocabulary word, and not hard to pronounce. (Ah-leel.) Here’s what you need to know about alleles:
There is room for exactly two alleles per gene in any given individual. A dog may have GG or Gg or gg, but never just G or g. A single dog cannot have GGg or ggg, either. An individual gets exactly two alleles per gene. This is important. An individual inherits one allele from its mother and one from its father. This is also important.
Two alleles of each gene per individual.
One allele of each gene from each parent.
It’s possible for all the dogs in a breed to have the same allele for a gene. For example, all Golden Retrievers are ee (gold). There are no E (non-gold) alleles present in this breed. When this is the case, the allele is said to be fixed. You don’t need to know that term particularly, but there it is.
It’s possible for there to be more than two alleles of a particular gene, although any given individual can only have two. In dogs, for example, there are four possible alleles for the spotting gene:
S (solid colored, like ruby or black-and-tan Cavaliers)
si (Irish-white pattern, as in Bernese Mountain Dogs, Collies or flashy Boxers)
sp (piebald white pattern, like blenheim and tri Cavaliers)
sw (extended white pattern, as in Clumber Spaniels or Great Pyrenees)
The superscripts are used, annoying as they are, because you need something other than just big and little letters if you want to identify more than two alleles per gene. Note that all of the alleles for the same gene usually get the same basic letter of the alphabet.
An individual will still have exactly two alleles for this gene. Thus:
A black-and-tan or ruby Cavalier could be SS or Ssp
A blenheim or tri Cavalier will be spsp
Dominant – an allele which “covers up” another allele from the same gene. In dogs, the B allele, which allows black pigment to be expressed, is dominant to the b allele, which dilutes black to brown, thus producing chocolate Labradors and red Dobermans. BB and Bb labs are equally black, so this trait would be said to be completely dominant. A Bb dog would be said to be carrying the b trait or the b allele, while a BB animal might be said to be pure for black or clear of brown. In the same way, solid color (S) is dominant to the alleles that code for increasing order of white -- for the spotting series above, dominance is more or less in the order that the alleles are listed. Alleles that code for less white "hide" alleles that code for more white.
Recessive – an allele which is “covered up.” The b allele is recessive to the B allele. All labs that are chocolate must be bb -- if a B allele was present, they would be black. Likewise, a blenheim Cavalier must be spsp -- if it had a S allele, it would be a wholecolor. The term recessive has nothing to do with whether a trait is good or bad, or how frequent the trait is a family or a breed. The blenheim color is by far the most common Cavalier color, for example. Recessive alleles often get lower-case letters.
Genotype – what alleles an individual actually possesses. BB is a different genotype than Bb, which are both different from bb.
Phenotype – the physical appearance and visible characteristics of an individual. GG and Gg dogs have the same phenotype (they are both gray). However, gg dogs have a different phenotype than either of the others (they are not gray).
Homozygous – both alleles possessed by an individual are the same; that is, BB and bb individuals are both homozygous. These dogs might be referred to as pure or non-carriers or true-breeding or clear for brown. You might see any of these terms used to mean homozygous, especially when referring to homozygous dominant animals. That's because homozygous dominant animals are the ones you need more information about (is this black lab carrying chocolate?) -- you always know what alleles a homozygous recessive animal possesses because they are visible (this chocolate lab is chocolate). BB animals are the ones called homozygous dominant, and bb animals may be referred to as homozygous recessive. These are more technical terms that mean the same thing as “pure.”
Heterozygous – the individual has two different alleles for a particular gene; that is, Gg. These individuals might be referred to as carriers for the little-g non-gray allele.
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There you go, that's enough vocabulary to get started. The most serious departure from reality in the above is the suggestion implied by all those definitions that most traits are controlled by single genes. In the real world, most traits are controlled by more than one gene acting simultaneously, and the breeder who does not have a thorough understanding of how to handle such polygenic traits in a breeding program is liable to run into trouble.
Lots more on the practical side of things given elsewhere on this site, but let me mention here that a trait is probably simple (caused solely or primarily by one gene) if:
-- it is known to be simple in other breeds / species,
-- it is easy to visualize as caused by a specific enzymatic pathway,
-- it is not anatomically complicated (eg, the shape and style of the head is complicated),
-- animals either have the trait or they don't (eg, the animal is either black or it isn't),
-- the trait is very consistent in presentation (eg, all dwarf malamutes are equally dwarfs),
-- and the trait doesn't appear to be affected much at all by environmental factors.
Of course, a trait is likely to be genetically complicated or controlled by non-genetic factors to the extent the above characteristics aren't true.
Like everyone else, I’m inclined to use canine color genetics to explain how genetics works, with references to genetic diseases where that would be useful. I’m going to focus more on using color to explain genetics, rather than offering a complete description of how color genetics actually works in dogs; if you’re interested in that – and it’s great fun – check out these links.
http://www.people.fas.harvard.edu/~brown/dogs/genetics/color2.htm#agouti
http://bowlingsite.mcf.com/Genetics/ColorGen.html
And, in my opinion, one of the all-time great color genetics sites, with some really fine thought-provoking articles . . . please give it a try if you're interested in the subject of color genetics, even if you're only interested in owning and breeding mammals:
www.birdhobbyist.com/parrotcolour/
And, incidentally, Phillip Sponenberg has the greatest book out (Equine Color Genetics) -- I learn something new every time I re-read it.
Lots of genetics books and sites meant for dog people contain information on color genetics, but no matter what sources you examine, you will find disagreement about which alleles are really present at which loci. Please remember that the study of color genetics is relatively new and that there's lots to be done before we have definitive answers about exactly which gene controls dominant black or where the brindle allele actually is!
All right, then, let’s jump right in and get our feet wet:
How Single-Gene Inheritance Works
The gene that sets base color in dogs is the agouti gene – the same gene that sets base color in horses and cats and mice, incidentally, if you find that sort of thing interesting. Here are the alleles for this gene that seem to me to most likely exist in dogs:
Ay = red sable (red hairs tipped with black; a sable collie is a good example).
as = saddle black-and-tan (Airedale)
at = black and tan (like a Rottweiler)
a = recessive black
Other alleles may exist for this series, such as gray sable (Norwegian Elkhounds) or dominant black (a very common allele in dogs -- but to which gene does it belong? No one is quite sure . . . ). It's within the realm of possibility that recessive black does not exist at this locus, for that matter. But let's take the above series as good enough for purposes of illustration.
All Cavaliers, like all Rottweilers, are black and tan (at at). That is the only base color present in this breed. They get their color variation from other genes. Let’s desert Cavaliers briefly to look at a breed that’s more interesting at this locus.
We'll use the Shetland Sheepdog, can be red sable, black-and-tan, or black, and we'll say that all these colors are controlled by the agouti gene. Recessive black is thought to exist in shelties, so this is at least plausible.
When you consider the agouti gene for sheltie, a sheltie could therefore be:
Ay Ay = homozygous for red sable. at at = homozygous for b&t
Ay at = red sable carrying b&t at a = b&t carrying black
Ay a = red sable carrying black a a = homozygous for black
Why can’t a sheltie a Ay ? Because dominant alleles are listed first. It’s a tradition.
Suppose you have a red sable sheltie bitch. What’s her phenotype? Red sable. What’s her genotype? You don’t know – not just by looking at the bitch. She could be pure for red sable or she could be carrying black-and-tan or she could be carrying recessive black.
Suppose this bitch had a black mother and a red sable sire. Now do you know her genotype? Yes, you do. Here’s the inheritance part:
First, this bitch must have at least one Ay allele, because if she didn’t, she wouldn’t be red sable. Second, she must have an a allele because her mother must have given her one allele and the only kind of allele her black mother had to contribute was the a allele.
That was important.
The mother must pass one allele of each pair on to her offspring. The father also contributes one allele of each of his pairs of alleles. Here’s our situation again:
Mom Dad
aa Ay _
Our Bitch
Ay a
Why is there a blank for the sire? Because all you know about him is that he was red sable. He could have had any kind of allele in that blank space and he’d still be a red sable dog. He did contribute a red sable allele to his puppy though, because she got that allele from somewhere and it wasn’t her dam. Her dam gave her a black allele. Her dam had to give her one allele, and black is the only type of allele she can give.
Suppose you cross your red sable bitch to another red sable sheltie and get six red sable puppies and two black puppies. What do you know about your bitch and the sire? You know that they must both have been carrying the black allele.
Mom Dad
Ay a Ay _
6 Puppies Ay _
2 Puppies a a
Some of the puppies are black (the sable puppies tell you nothing -- it's the most recessive type that tells you the most). The black puppies have two a alleles or they wouldn’t be black. One of those alleles must have come from the mother, so she must have an a allele in her blank spot. The other must have come from the father, so he too must have an a allele in his blank spot. Puppies get one allele from each parent. Both parents are thus proven or obligate carriers for the black color.
Departing for a moment from coat color, let me add that exactly the same logic works for simple recessive genetic diseases. If you’re lucky enough to have a genetic problem in your breed that is a nice, simple recessive, such as copper toxicosis in the Bedlington Terrier, then you can pretty easily learn information about the dogs in your breeding program. Suppose you have a puppy with copper toxicosis in a litter from two normal animals:
Mom Dad
T _ T _
Puppy tt
Where did this puppy get its little t alleles? Well, obviously, one came from Mom and one from Dad. Both are obligate carriers. Can you safely breed these animals again? Sure, but not to each other -- go take a look at the practical genetics pages for lots more on the practical aspects of making breeding decisions.
You also can make guesses about the siblings of this affected puppy. The most typical way to show this is with a Punnett square, like this:
| T | t | |
| T | TT | Tt |
| t | Tt | tt |
Mom's alleles are listed one at a time down the side and Dad's across the top, bolded. The ways these alleles could possible match up in puppies are shown in the other boxes. You just carry Dad's down and Mom's across to fill in the puppy boxes. Either a puppy gets two big T alleles, one from Mom and the other from Dad, or it gets a big T from one parent and a small t from the other parent, or it gets one little t from each parent. There is one box out of four with a TT genotype, two boxes with Tt genotypes, and one with a tt genotype. All the puppies with at least one big T have normal phenotypes -- they look normal. Only the tt puppy shows copper toxicosis.
You can read these boxes most effectively as chances per puppy born from these parents. There is a 1/4 chance (one box in four) that any puppy conceived will have a TT genotype, a 2/4 = 1/2 chance that a puppy will have a Tt genotype, and a 1/4 chance that a puppy will have a tt genotype. A puppy from this mating has a 3/4 chance of being normal. There are three normal boxes, so a normal puppy from this mating has a 1/3 chance of being pure TT and a 2/3 chance of being heterozygous Tt. The risk that a normal sibling of an affected puppy is a carrier of copper toxicosis is 2/3.
If all this is clear so far, you're in fine shape. If you want a more in-depth look at how to use Punnett squares, or if you want to see how to quickly figure probabilities without using Punnett squares, go here.
Back to Cavaliers and color. Let us add a tiny complication. Obviously all Cavaliers are not really black and tan. Why not? Because other genes affect the expression of color, that’s why. In Cavaliers, the other important gene involved in color is the extension gene. This gene may also have multiple alleles, but there are only two that matter for Cavaliers:
E = no effect on the agouti gene.
e = clear golden or red (no black tipping on the hairs)
The e allele at this locus is responsible for the golden color of Golden Retrievers, the solid red of Irish Setters, and the red of ruby and blenheim Cavaliers. Modifying genes control the shade of the dog, which can range from cream to dark chestnut red (breeders prefer Cavaliers on the dark side of this range). Regardless, we know that all red Cavaliers get their color from the ee genotype.
So Cavaliers have only a few possible genotypes:
at at EE = black and tan
at at Ee = black and tan
at at ee = ruby
Note that although people often refer to black-and-tan as “dominant” to red, this is a sloppy and misleading way of putting it because it’s not a dominant allele at the same gene. These are two different genes and one can’t be dominant to the other. Really black-and-tan, although a recessive color at the agouti locus, is always there, and the E “not-red” allele is dominant to the red e allele. The E allele doesn’t create black pigment, it just allows black pigment to be expressed if the agouti gene says it should be (which in Cavaliers it always does). We would say that the ee genotype is epistatic to any color otherwise coded for by the agouti gene. That means when ee is present, regardless of what genes are present at the agouti locus, the dog will be red. Okay?
Onward –
Broken colors are then formed by adding the third main gene that affects Cavalier color, which is obviously the spotting gene.
at at E_ S_ = black and tan
at at E_ spsp = tricolor
at at ee S_ = ruby
at at ee spsp = blenheim
There are all kinds of interesting dilutes that Cavaliers don’t have: the D series dilute that gives us blue Italian Greyhounds and Great Danes; the B series dilute that gives us chocolate Labradors (both dd and bb at once gives the odd but beautiful Weimerainer color); the gray allele that gives us the beautiful Kerry Blue Terriers, the incompletely dominant chinchilla dilute (cch) that gives us palomino, buckskin and cream horses and probably some of the creams and whites that we see in dogs, and the less-fun dominant merle that gives us merle Collies and has to be handled carefully because it can also cause nasty vision and hearing defects. There are a couple of other alleles we sometimes see in Cavaliers but don’t want, such as the dominant ticking allele that gives the Dalmation spots and makes English Setters belton. Line them up and we have our beautiful blenheim Cavalier, for example:
at at ee spsp BB DD CC GG mm tt
This animal is black-and-tan, diluted to red by the extension allele, color broken by the spotting allele, not-brown, not-blue, not-chinchilla, not-gray, not-merle, not-ticked.
The only variation comes from the extension and the spotting genes. All the rest of the genes are fixed in this breed. And people say that color is complicated in Cavaliers! This is complicated? Try Poodles, Salukis or Great Danes.
It’s easy to work out what colors ought to produce what in Cavaliers and everybody’s done it. Why should I add to the list? I’ll leave that as an exercise for the student. To prompt the student to try, here’s a list of homework questions (okay, solutions here if you must check).
What’s the genotype of a tri dog if all his puppies are always either black-and-tan or tricolor?
What kind of cross will always give nothing but blenheim puppies?
If a black-and-tan bitch has one puppy of each color, what is her genotype and what can you say about the genotype of the stud you took her to?
If a blenheim puppy was produced by a blenheim bitch mated to a tri male, what was the genotype of the male?
If a ruby bitch mated to a blenheim produces a tri puppy, does this mean that some other male must have gotten to her when you weren’t watching?
If you want to find out whether a tri dog is carrying red, what should you breed him to?
Of course, in reality, our neat little Mendelian single-gene assumptions get rather complicated! On to the real world --