Genetic Literacy, Part I
(or: of Doghouses, Bad Blueprints, and Too Much Beer)
(c) 1991 Mark Martin
Last Labor Day, I made the Third Annual Mark Martin
Mental Health Pilgrimage to Portland for the 1991 CRNC Water Test (I was
disappointed to find that energy crystals and their ilk were in use in
the Northwest, too---so New Ageism is hardly a Californian problem!).One
evening, I had dinner with the editors of the CRNC NEWS (we
own littermate Newfies, which makes us relatives in an odd fashion). Over
some too-healthy Lebanese food, we discussed the fact that very few dog
owners know anything about genetics. Some of these people are breeders,
and become saddened by the increasing incidence of genetic defects in their
kennels over the years. Others purchase puppies without detailed knowledge
of the pedigree of their new dog, and sometimes end up with an unstable
or unhealthy puppy. Both categories of people are losing---big time---because
they do not have a simple working knowledge of genetics, both its predictive
powers and its limitations. Dr. George Padgett of Michigan State calls
this "genetic illiteracy."
Let's look at a couple of examples of genetic illiteracy. At a dog show once, I had an earnest and intelligent individual---a dog breeder, in fact---walk up to me and very seriously ask "where in the body the chromosomes are located" (and, by the way, don't be worried if you don't know what a chromosome is, let alone where one might be located---the answers are pretty simple). And most of us have heard a person say that dog X "carries" genetic disease Y, but isn't affected by the disease, so it would be all right to breed dog X. Is it? How do you know? How do you, as a prospective puppy buyer---or even a breeder---evaluate a dog in terms of its genetic heritage and potential?
Most of us just shrug our shoulders and hope for the best; we buy the cutest puppy, we breed the dog with the most ribbons and plaques. We don't speak the language of genetics, and have decided that it is far too tough a topic for us to understand. That attitude is simply wrong, yet easily corrected by a little reading and thought.
In any event, back to dinner in Portland last summer. The editors of the CRNC NEWS asked if I might write a column for the newsletter concerning genetics, since genetics is what I do for a living.
Let's talk about me for a second.I have earned a bachelor's degree in Biology, and a Ph.D. in Biological Sciences (specializing in molecular genetics). I have worked in genetics for over ten years, and have taught courses in the subject at the university level. My research involves the genetics of bacteria (because I am squeamish, I suppose; bacteria don't have fur, really aren't terribly cute, and I can literally raise a hundred billion of them in a test tube overnight), so a reader or two might question my qualifications to write about genetics in higher organisms. But the beauty of genetics, you see, is its sheer generality. The basic principles of DNA, gene expression, recessiveness, and environmental effects---they apply to all living things, from bacterium to redwood tree to virus to blue whale to parakeet to human.
I have no intention of treating this column as a college seminar, full of jawbreaker terminology of Latin descent.Remember that several ancient cultures created the myriad breeds of dogs from something very like a wolf, over the past six or seven thousand years---without even knowing the concept of a gene, let alone all that science has learned about genetics over the past century. That one nondescript canine ancestor was used to produce---with careful selective breeding---such diverse breeds as Bulldogs, Schipperkes, Mastiffs, Pugs, Irish Wolfhounds, Basenjis...and Newfoundlands. All in a few thousand years (and remember that the ancient Egyptians had dogs that look identical to Salukis, five thousand years ago!), without veterinarians, stethoscopes, "designer dog chows," and cellular telephones. My point is that you don't need a Ph.D., or a B.A. for that matter, to understand the basic concepts of genetics. You don't need high technology, either. You see, much of genetics is common sense.
If you read this continuing column, you will find that genetics is not such a tough subject after all.You may even pick up a short textbook or two on the subject---and be well on the road to true genetic literacy.I don't mean to imply that this column will teach you everything you need to know about genetics---it is intended as an introduction, a springboard, to spark your interest in the subject.The more you read, the more you think and reason, the more genetically literate you will become.As a breeder, you will be able to produce better, healthier puppies.As a buyer, you will be able to ask the right questions of a breeder, and make informed choices.
* * * *
There is much more to genetic literacy than dog breeding, too. I guarantee that all of you reading this column, as voters, will be asked to help shape laws the control, restrict, or encourage genetic research: crops genetically engineered to resist pests or produce higher yields, modified vaccines to protect against diseases, and consumer products manufactured from genetically engineered microorganisms. The problem is still larger, actually, because you will, in the next few years, be asked to decide on laws which involve how genetics can interact with our lives as citizens in a legal sense. For example,can DNA "fingerprinting" be used to prove that a suspect ---a rapist, for example---actually committed a crime? Or:if a person can be shown, genetically, to have a predisposition toward alcoholism or mental disease, should such a person pay higher insurance rates? There will be a lot of nonsense spread on both sides of such issues, by individuals and organizations with political axes to grind; you will be able to evaluate the facts of such issues apart from the political rhetoric---if you are genetically literate, that is.
"Oh, brave new world, that has such things in it," and all that sort of language found in pretentious Shakespearean quotations. The point is, genetic literacy is important, to all of us, not simply to researchers or dog breeders.
In this column, I will provide the basic framework for an overview of genetics. It will be far from detailed. Yet as the 19th century physicist Lord Kelvin once wrote, "If one cannot explain what one does to the lay public, then it is probably not worth doing." And he is quite right, in my opinion. By the way, for those of you well-schooled in formal genetics:please forgive my oversimplifications in the first few columns. I believe that, initially, concepts are more important than details. So bear with me.
For this first outing into the world that the19th century introverted Austrian monk Gregor Mendel described using the lowly pea plant---formal genetics---I am going to describe a very simple scenario that we will come back to again and again in future columns.I want you to forget about dominant or recessive traits, meiosis, aneuploidy, holandric genes, DNA replication, protein synthesis, pleiotropy, or multigenic characteristics.These are all twenty dollar words that exclude the layperson from just how easy genetics can be. Once the framework, the concepts, are firmly established, we can come back for details and for a specialized vocabulary. Fair enough?
I want to start with a doghouse, of all things.
Anytime any building is constructed, a detailed blueprint is required. The blueprint shows the location of every wall, every window, every electrical outlet. A construction crew follows that blueprint to the letter---without question or comment (unlike a real-world construction crew, I suppose)---and begins building the structure according to those on-paper plans. The environment can effect how well the construction crew follows the blueprint, obviously: are there enough building materials present, does bad weather damage the structure under construction, is the crew even competent to work, and so on.Finally, the construction crew, following the blueprint, provided the environment is right for building, finishes the structure. Walking down the street, all you see is the finished product, right?
That is what is shown in Figure One.
The goal is to build a doghouse. The blueprint contains all the information
needed to build the doghouse. The construction crew follows those
instructions, provided the materials, workmanship, and weather permit the
work. The finished product is good old Fido's new home.
Yet the workers can only follow the blueprints, and quite blindly, at that. If there is a mistake in the blueprint, the final structure usually has mistakes, too.That is the situation in Figure Two. We can call the tiny mistake in the blueprint a "mutation." The workcrew is wonderful, there are plenty of materials, and the weather is fine.They follow the incorrect instructions, not knowing there is anything wrong, and build the defective doghouse with half a door. We can call it a "mutant" doghouse.
I can tell that many of you know where this is going.Please bear with me.
What if the blueprint is absolutely correct? Could something still go wrong?Of course; the weather could damage the doghouse under construction, some of the necessary building materials could be out of stock, or the construction crew could be incompetent. The blueprint is perfect---it is the execution of the "building plan" that goes awry. This is the situation in Figure Three. In this example, the construction crew has had way too much "Vitamin B," and therefore makes a simple mistake while building the doghouse---the "F" in FIDO has been flipped. As you might guess, a sufficiently drunk construction crew could leave out the door entirely; the mistake mentioned is very minor compared to what might have happened.
Note that the mistake in Figure Three is NOT due to a mutation, even though the finished product looks wrong. The blueprint is perfect. Yet the defective doghouse looks like a mutant, doesn't it? The ten dollar word for this phenomenon, by the way, is a "phenocopy" of a mutation. The "environment," not the "blueprint," is the source of the trouble. How can one tell the difference? Well, since the blueprint in this example has no mistakes at all, making another doghouse---provided there is no beer around, this time---will result in a normal doghouse. In terms of dogs, instead of doghouses, such a supposedly "mutant" dog gives rise to perfectly normal puppies, over and over again---because the blueprint is completely correct. More about that in upcoming columns.
Figure Four shows how the examples discussed
above relate to genetics.The "blueprint" is made up of genes, composed
of the chemical, DNA.All of the genes, together, comprise the blueprint
and instructions for construction, collectively called the genotype.
These instructions are carried out by our biological machinery (instead
of our drunken construction crew in Figure Three). The machinery
can be influenced by the environment, in ways similar to the examples
mentioned earlier.So, the genotype and the environment, acting together,
result (after "construction," of course) in the final product. The
final product---what one sees---is called the phenotype. But
remember:sometimes, the environment can negatively influence the way that
the genotype is expressed, leading to what looks like a mutation;
the genotype is unchanged and completely correct (and such a false mutation
will not occur again, provided the environmental influences are no longer
And there you have a simple version of how the DNA inside a single fertilized egg (a blueprint or genotype), interacting with the environment, results in a final product that we see---the phenotype of an intact organism (i.e., your bouncy and busy Newfie puppy, all dark eyes, fluffy fur, and wagging tail). Generally, the terms genotype and phenotype are used to describe a small set of genes and their final results. For example, a Newfoundland's coat color---the observed final product, or phenotype---can be gray, brown, Landseer, or black. Yet we know that some black Newfoundlands "carry" genes for Landseer coat color; such dogs are genotypically "mixed." We don't "see" the genotype---we can only infer its nature from what we do "see" in multiple breedings, the phenotype.
Which brings us to the next column:chromosomes, alleles, recessive or dominant traits, and a few other things.We will be using coat color as an example, just as we used a mythical doghouse as an example in this column.
What are the important issues in this column? The
genotype. The phenotype. Mutations. How the environment can alter
the expression of the genotype, leading to what appears to be a mutation.
This latter item is important; if you have a dog that appears to
have a defect---but due to the environment instead of mutation---he
or she could be used in a breeding with impunity. Yet how to tell
the difference? As stated above, a mutation will "breed true" (the
problem would repeatedly crop up in related breedings, though I am oversimplifying
here) while an environmental defect would be a one shot problem not appearing
in related breedings. This is one reason why complete and honest
information on the pedigree of a dog is so useful to both prospective breeder
and buyer.It is also why some individuals are not totally honest when discussing
their dogs. Dr. Padgett calls this the "questionable sociology of
* * * *
I have a lot of rather sloppy
and unprofessional diagrams for this column, so I will split this essay
into two sub-parts --in the interests of newsletter space requirements
(and maintaining your attention, of course). Bear with me.
This column will be observation oriented - showing you all what happened
in the hypothetical breedings described below. The next column will
explain why those things happened.
Last column, we spent some time on the concept of the phenotype (what you see) versus genotype (the unseen genetic blueprint for the trait in question). And I used a fairly simplistic model for these concepts of blueprints and environment working together-the construction of a doghouse. We discussed how the blueprint itself could be faulty (a mutation), which after construction resulted in a defective doghouse (a mutant). Additionally, it was shown that the blueprint could be perfectly copacetic, yet the environment was such that the blueprints were not followed correctly, leading to an apparent mutant doghouse (a phenocopy). By the way, the only reason I brought up the idea of the phenocopy was to drive home the point that the environment has a strong influence on how the genotype, or blueprint, is expressed (followed). In fact, a phenocopy mimics a mutation, even though the genotype would be completely normal and unaffected.
Let's get a little more specific in this column. In fact, let's talk dogs, instead of doghouses Naturally, this being the CRNC NEWS, I would like to discuss Newfoundland dogs.
Incidentally, in the diagrams that follow, I did my level best to draw decent Newfies. They may look like mutant rats or dwarf cows to you, but I traced (with a seriously caffeine afflicted hand, I freely admit) from the Breed Standard Booklet as best I could. Which ain't much, I know.
In other words, my apologies to: the breed standard, breeders, dog lovers, and artists!
Newfoundlands, as we all know, come in several flavors
of color variations: black, grey, bronze, or Landseer. In the interests
of clarity (and because of the monochromatic nature of the CRNC NEWS),
I decided to use the black versus Landseer coat color "types," or...you
guessed it ... phenotypes.
Before we move on, I fully realize that many of you have read about the topics in this column before, in college or even Mark Martin in high school (although my New Math high school did not mention genetics at all). So, for some of you, this column is obvious and old ground. Still, let's all start at the same place, so that we can all end up with the same degree of knowledge and information, regardless of the often dubious quality of our wonderful government supported educational programs. OK?
Figure One shows a cross between two black Newfoundlands. By the way, forgive the unimaginative names - I have a lot of hypothetical Newfies to name in this column, and my brain hurts! The four Newfies below the parents represent the four puppies that were produced from that mating (or in genetic parlance, from that cross). I am also assuming two males and two females in each litter of puppies. Litter size and distribution of sexes are not important right now - this is a hypothetical breeding. In any event, notice that both parents are black-and so are all four puppies. Fair enough, right? Like begets like.
Figure Two shows a cross between two
Landseer Newfoundlands. Notice that all four puppies also display
the Landseer coat color phenotype.
So far, so good, right? All of this makes sense.
Let's get just a trifle tricky, shall we?
Figure Four shows you that the above
idea is not always correct. A black bitch and a black dog are crossed,
and three of the four puppies are black. Good news, as expected.
But the fourth puppy is a Landseer! Yet both parents were black ...
and the "black coat color" programming always wins out over the Landseer
color trait, as we observed in Figure Three Doesn't it?
It looks as if one or both of the black parents in Figure Four were somehow "carrying" an invisible Landseer coat color blueprint. Playing along with this idea, the "invisible trait" would be passed down (from Zelda and Zach) to one or more of the puppies - but the hidden trait was somehow only activated in little Quentin. Sure, all of that seems like a bit much. Yet such an odd chain of logic is part of the answer - both of the parents are carrying an invisible Landseer coat color blueprint (and more about this, of course, in the next column).
The interesting part of the above discussion is that Gregor Mendel, the 19th century Austrian monk who first described the "laws" of genetics, made very similar observations in his monastery garden. Except that Mendel didn't use Newfies in his simple experiments; he used the common pea. He noticed that some peas were wrinkled, while others were smooth. Mendel did Several experiments, "crossing" the pea plants (sure, plants can have "sex," too - whether or not they enjoy it is unknown) produced by those smooth or wrinkled peas, just as you and I hypothetically crossed the Newfoundland dogs in Figures One through Four. Mendel discovered that the wrinkled and smooth "phenotypes," or "pea traits" in his plants behaved in an identical fashion to the black versus Landseer coat color traits in the canine matings above. Remember what I wrote, a while back, about the universality of genetics? Peas and puppies-you cannot get much different than that, can
you? Yet the same genetic "rules" seem to hold in both-very different cases.
Personally, I don't care for nasty crunchy vegetables. And Newfies are much more fun to be around - and cuddlier in the bargain - than pea plants. Still, it is much easier to raise a lot of peas than it is to raise a lot of Newfoundland puppies, yes? The easier it is to raise a living thing for these kinds of experiments, the more experiments can be done. Which is why we know a lot more about bacterial, fruit fly, pea, and mouse genetics than we know about canine genetics. Next column, I will explain precisely what went on in Figures One through Four above. But I need to give you a bit more "diagrammatic vocabulary." Hang in there, because we are almost done now.
Figure Five shows several things of interest. First, that dark circles or squares represent black Newfies, and open circles or squares represent dogs displaying the Landseer color trait. Also, notice that circles are girls and squares are boys (what else is new, I hear some of you ladies muttering). The bottom part of the figure shows both Figures One and Two in this newfangled circle and square format. Notice how coat color and sexes are represented in the new format.
1. What kinds of puppies do you expect when you breed puppy bitch Tina to puppy dog Quentin? Let's ignore close inbreeding for now, OK?In this column, we have discussed the ideas of dominance (the black coat color trait in Figure Three), recessiveness (Landseer coat color in Figure Three), and "hidden" traits (the mystery Landseer that popped up in Figure Four).
2. What kinds of puppies do you expect when you breed puppy bitch Rona to puppy dog Quentin? (by the way, you are right: I did leave out one type of breeding from the Figures One through Four group - do you know what it is?).
3. What is the only way to know if your black Newfie "carries" the Landseer coat color trait (suppose he or she is a "rescue Newf," and you know nothing about his or her ancestry)?
Genetic Literacy, Part III
(Or: Of the Birds and the Bees, the Newfies and the Genes; Sex and the Single Pedigreed Newfoundland;
Punnett Squares, Heterozygotes, and Why There are Two Kinds of Black Newfies)
(c) 1992 Mark Martin
This issue's Genetics Column will cover lots of little
items, and have a touch of philosophy as well. I am well aware that many
of you are familiar with the technical topics that I will shortly be discussing,
but I want all of us to be at the same level for future, more complex columns.
OK? Last time, I showed how two black Newfoundlands could produce a litter
of mixed Landseer and black puppies. I moved the column from my child-like
illustrations of Newfies to a more traditional "genetic nomenclature" of
circles and squares, filled and open and half and half. Remember? Let's
get detailed. All living things are made up of cells, and within each cell
exists the basic master plan, or blueprint, which is made of DNA. DNA is
a long, thin string of a molecule---in fact, if the DNA contained in just
one of your skin cells was stretched out, it would measure about four feet
long. No kidding. This relatively enormous length is packed into a tiny
cell that you can't even see without a microscope. That takes some serious
packing, as you might imagine. In fact, the total DNA blueprint is not
contained in one molecule, but broken up into separate little bundles (presumably
to make them less fragile as well as easier for the cell to work with---like
during cell division!).
Those bundles are called chromosomes.
It is as if that master plan, or super blueprint, is too big to be handled easily---during either copying (cell division) or when being read by the contractors (when the DNA instructions are being followed by the cell). So, for utilitarian reasons, that blueprint is parcelled out into the small bundles called chromosomes. Every single cell in your body, from brain neuron to bone marrow cell to skin cell to muscle cell---billions and billions of them---each have a complete copy of the master plan.
Remember the question: where in the body are the chromosomes located? You now know the answer. Everywhere.
Chromosomes come in pairs. Why would that be so---it just seems like extra work, right? Suppose you only have one copy of the blueprint, and a mistake was made during copying (a mutation, remember?). Well, that part of the blueprint is now defective. It might not be a real problem (imagine your skin without pigment, for example) but it could well be lethal (what if the "heart construction section" of the blueprint was ruined?). A "good" copy of a gene can often overrule a "bad" or defective copy---a major advantage to having pairs of chromosomes carrying genes.
Now you can begin to see how a black Newfoundland can "carry" a hidden Landseer trait- --such a dog contains two copies of the coat color blueprint...and the "black" blueprint takes precedence over the "Landseer" blueprint. More about that in a future column. As I mentioned earlier, chromosomes come in pairs. You and I possess 23 pairs of chromosomes---46 in total. An annoying mosquito has a mere six chromosomes, and a carp has a staggering 104. Dogs have 78 chromosomes, or 39 pairs.
Figure One is the story of good old Zelda and Zach from last time. Figure Two illustrates their happy family in more traditional genetic nomenclature (sorry to
We will get there, probably next column. Remembering
Three, let's focus on that one chromosome pair. Figure Four
shows Zelda, Zach, and their family---both as my chimp-handed artistic
representations and as "chromosome pairs." Notice how both "BB" and "Bb"
dogs are black; this is the descriptive basis for recessive and dominant
traits, as we have been discussing. "BB" and "bb" dogs are called homozygous
(identical copies of the part of the genetic blueprint in question), while
"Bb" dogs are called heterozygotes (different copies, natch).
Now we have to discuss Sex and the Single Newfoundland.
At the risk of sounding as if I am writing a performance grant to the National Endowment for the Arts (heads up, Jesse Helms!), dogs reproduce by fusing sperm and eggs---just as you would expect. But enough about sex and conception. Think about those chromosomes contained in the sperm and egg for a minute...if a dog has 78 chromosomes in every cell--- including sperm or egg---we have a numerical problem, don't we?
Sperm (78 chromosomes) plus egg (78 chromosomes) equals---eventually---a puppy. Does that puppy have 156 chromosomes? And what about when that puppy has puppies?
We would be knee deep in chromosomes in no time. But nature does not allow that to happen.
The cells in the body that makes sperm and eggs ("gametes" for the fastidiously minded) contain 78 chromosomes, but sperm and eggs those cells produce have half that number, or 39. Now you see another reason that chromosomes come in pairs. This process of "reduction division" during "gametogenesis" (the process of producing sperm and eggs) is called meiosis. Normal cell division (not involved in the production of gametes), on the other hand, is called mitosis. Let's focus on that chromosome pair that contains the coat color locus. If only half of each pair of chromosomes goes into a sperm or egg...then the sperm or egg has to make a choice, since they can only hold one chromosome from each pair. This is no problem for a "BB" or "bb" dog---so far as the chromosome that contains the coat color blueprint, there is no choice. Only one kind of sperm or egg is produced. For "Bb" dogs, two kinds of sperm or eggs are produced. Half of the sperm or eggs in this case contain the "B" chromosome, while the other half contain the "b" chromosome.
Now, lets look at Figure Five---again, with Zelda
and Zach---and bring it all together. Again, forgive my bizarre representations
of sperm and eggs---though Woody Allen would be proud of me. Zelda makes
two kinds of eggs, "B" and "b," just as Zach makes two kinds of sperm.
See how the sperm and the eggs fuse in four ways, to yield fertilized eggs
(and eventually, puppies) with the normal complement of 78 chromosomes
total? This representation in Figure Five, by the way, is called a Punnett
Square, and helps the budding geneticist determine phenotypes and genotypes
in a cartoonish kind of manner. We have only examined one chromosome pair,
the chromosomes that possess the coat color region of the total dog genetic
blueprint. Yet the same basic principles described above apply to all 39
of the chromosome pairs contained in every cell in every dog on earth---including
your own Newfoundland. Now you understand the True Story of Zelda and Zach.
And with a little thought, you should be able to figure out the other matings
in the last column, too. Can you draw up Punnett Squares for those matings,
Let's look at the questions I posed in the last column for a moment. When Quentin and Tina have puppies---you get an all black litter, just as seen last time for Yvette and Yarrow. Quentin and Rona? You get a half black, half Landseer litter, as shown in Figure Six, complete with Punnett Square.
The third question from last issue's column
is pertinent: how can you know if your black Newfie "carries" the
Landseer trait? That is, is your black beast a "BB" or "Bb" kind
of dog? The only way to be sure (imagine that you obtained your
dog from Newf Rescue, and have utterly no idea of the animal's ancestry)
is to do a "test mating." No, that isn't some arcane Californian
sexual aberration (or if it is, I haven't heard of it, which I don't suppose
means much). Simply cross your "mystery" black Newfie to a Landseer
Newfoundland (yeah, yeah, of the opposite sex). Then look at the
resultant puppies. If they are all black, your mystery Newf had to
be of the "BB" variety, right? And if your "test" litter is half
black and half Landseer, then you know that your mystery pooch is a "Bb"
kind of dog. It makes sense. We will be returning to the concept
of "test crosses" (remember that geneticists use the more antiseptic term
"cross" instead of the down and dirty word "mating") in later columns,
because test crosses are often the key to reducing the incidence of genetic
diseases in dogs and other animals. Whew! We have covered a lot of ground
this issue: chromosomes, meiosis, test crosses, heterozygotes, homozygotes,
and canine sex. I cannot promise such an exciting column next time---what
am I writing, canine pornography (."..Ginger licked her chops and quivered
seductively as Rover sidled up boldly; the test cross was mere seconds
away...")? Still, we are moving along to more complex subjects,
in what I hope is an informative and entertaining fashion. Hang in there!
One final word. Dr. George Padgett (who we will be discussing further in
later columns) is the guru of genetic disease control in dogs. One thing
that is basic to controlling genetic disease is complete and absolute honesty.
There are many breeders and owners out there who refuse to admit that their
own dogs and breeding programs might have flaws. Such people are more interested
in blaming other breeders for genetic problems than trying to improve the
breed. Padgett, in fact, urges prospective dog owners to be quite bold
on this subject---to ask the hard questions of breeders. And to not necessarily
believe what they are told. This is why Padgett has promoted the
idea of an open genetic registry---similar to (but more expansive than)
the OFA and its positive influence on the control of hip dysplasia.
Time and time again, I have seen people refuse to admit that their own breeding program has flaws (and every breeding program does, ladies and gentlemen), and attempt to blame a bad litter on the "other half" of the mating (especially in very valuable attempts to outcross). You have to ask yourself a very simple question. Which is more important: one's pride, or the good of the breed? When I was a boy, I used to breed fancy guppies (this was how I became interested in genetics, in fact), and had many friends with the same hobby. I loved developing a more vibrant blue color, or a more flowing fanlike tail in my fish. And I refused to admit to my friends that my crosses were producing greater and greater numbers of defective offspring (due to harsh and extreme inbreeding---I was in a hurry). I just flushed ‘em (one advantage to breeding tropical fish, of course). And when I would cross one of my prized fish to a friend's fish---attempting to outcross, to increase the genetic health of my breeding stock---I would sometimes get a profoundly defective batch of baby fish. Since my ego was so tied up in those silly fishtanks and their finny denizens, I would actually blame my friend's fish as the source of the problem. I didn't really know which fish was at fault, to tell the truth; I just wanted to blame someone else. Pretty soon, none of my fish raising friends would let me outcross to their stock; I had become a braying jackass. And my own breeding lines became more and more inbred, and produced more and more defective offspring. You can guess the rest. I don't breed fancy guppies anymore. And I don't want to see the same sort of thing happen to my beloved Newfoundlands. The health of the breed is much more important than mere ego, or should be, anyway. We will be returning to this point in future columns---all of us must work together, to control the genetic diseases that are becoming more and more apparent in Newfoundlands. It will take honesty, humility, and hard work. Think of the dogs, ladies and gentlemen. We owe it to them, in exchange for all they do for us, don't you think?
Genetic Literacy, Part IV
(Or: A Quick Breather and a Kinder, Gentler Review, with more
Detail on the Romantic Entanglements of Different Newfie Phenotypes,
Sex and the Single Cell, and Improved, Clarified Nerdish Nomenclature.)
(c) 1992 Mark Martin
Yes, OK, jawohl, si, da. I hear you.
The last column was confusing. First, I skimmed lightly over rather deep
information, and then there was a diagrammatic error during the preparation
of the last issue of the CRNC NEWS (Hey?you try putting together a entire,
professional looking newsletter quarterly, in your spare time, for free,
without any errors whatsoever. As my late grandfather used to say, "Talk
is cheap; whiskey costs money.") [NB: inadequate memory scrambled images
in the newsletter of Summer, 1992; that was fixed by a re-mailing, and
does not affect this web version.- mm].
So, this will be a short column, designed to reiterate most of the points in the last column, with greater clarity. This is important, because we start wading past the shallow part of the gene pool soon, so to speak, and we all need to be on the same level.
The "model system" we have been dealing with in this column is the inheritance of simple coat color in Newfoundlands?black versus Landseer (at this stage of things, anyway). A Landseer crossed with a Landseer always gives rise to an all?Landseer litter of puppies. But when a black is crossed with a Landseer, things can become a bit less obvious.
Some black-Landseer crosses give rise to all black litters, as we would expect if the black coat, or phenotype, is dominant over the Landseer trait. Yet some black?Landseer crosses (like the happy union of Rona and Quentin in the last column) give rise to a half black-half Landseer litter of wriggly puppies.
And, just to be more difficult, not all black-black crosses yield all black litters, as would be expected (since in terms of coat color, black is supposed to be dominant over Landseer). Some black- black crosses yield an odd litter: three quarters of the puppies black, and one quarter Landseer (as was the case for Zach and Zelda in the last column).
The reason for all of this oddness is that traits are inherited, both in dogs and dogwoods (and me and thee), as discrete units, or genes. We have been dealing with this concept for several columns, so it is nothing new.
The entire blueprint for a dog (or a killer whale, or a rosebush) is contained in a long string of a molecule called DNA. That blueprint is carried in every cell of the body, from nerve to muscle to hair follicle to ovary. And because that complex blueprint molecule, DNA, is so very long and unwieldy, it is condensed into an easy to handle form called a chromosome. A chromosome is simply a "packet" containing part of the total DNA of the organism. Dogs have 39 of these chromosomes.
Yet chromosomes of higher organisms come in pairs, for a large number of reasons both practical and philosophical (at least within the ivory towers of academia). It is sufficient to say in this column that keeping chromosomes in pairs helps protect the organism against bad mutations that could kill the creature in question, and to promote different combinations of chromosomes (some of which might be better than others in terms of survival, health, or other factors).
Dogs have 39 chromosomes (actually 78, since chromosomes -- again -- come in pairs), and we will now focus on just one of those chromosomes. We will call our selection chromosome 7, simply for convenience. Chromosome 7 is a packet of DNA, a portion of the total blueprint for a dog. Genes that control bits and pieces of that complete and complex blueprint are arranged on that piece of DNA -- hromosome 7 -- like beads on a string. And at a particular location on that chromosome, there exists that portion of the Total Dog Blueprint in control of coat color.
Yet chromosomes do come in pairs, as we have
been discussing, which means that there are two copies of chromosome
7. And that portion of chromosome 7, that gene which specifies
coat color, can differ: as we have seen, that region, or locus,
differs in Landseers and black Newfoundlands. These are not different
genes, since they are very, very similar to one another. They are variants
of one another, different forms of the same gene. We high falutin'
scientist types call these different forms alleles of the same genetic
region. The original form of that odd word was the even stranger term allelomorph
-- which is Nerd Latin for "different form." We already know that
black is dominant over Landseer ... what does that mean in terms of chromosome
Keep in mind, again, that "B" and "b" are NOT different genes, they are different forms of the same gene, alleles of one another, carried on chromosome 7. The dog has a full complement of chromosomes, which includes two copies of chromosome 7. Each chromosome copy can have a different allele ("Bb" genotype) or the same allele ("BB" or "bb" genotypes).
Figure Two shows how the different types of
dogs differ in appearance, or phenotype, and what that means in
terms of chromosome 7. Compare Figure Two to the diagrams of various Newfle
crosses described in last issue's column; don't they now make more sense?
Notice how, in a heterozygote (a dog containing both "B" and "b"
alleles on the two copies of chromosome 7), the "B" allele "masks" the
"b" allele, which can be silently carried along in a black dog. This is
how, in the last column, Zelda and Zach -- two black dogs -- could in fact
give rise to a Landseer puppy. Now do you see the nature of -- for
coat color, anyway -- dominant and recessive traits? If the dog carries
Landseer and black alleles on it's two copies of chromosome 7 -- think
of the alleles as blueprints controlling coat color?the "black coat color"
instructions supersede the "Landseer coat color" instructions.
As we discussed last time, the gametes -- sperm and eggs -- of animals do not contain a full complement of chromosomes. The nonreproductive cells of the body, the somatic cells, contain a full complement of chromosomes -- 78 for dogs. The reproductive cells (also called germline cells), sperm and eggs, contain just one copy of each chromosome, or 39 total. If it were not so, then somatic cells would quickly accumulate far too many copies of the original set of chromosomes after just a few generations.
There must be a method by which the full complement of 78 chromosomes in somatic cells is reduced to just one copy of each chromosome, or 39, in the reproductive cells. This process is called reduction division, or meiosis (as opposed to the process by which, say, a skin cell with 78 chromosomes divides to make a second skin cell, also with 78 chromosomes - which is called mitosis). Somatic cells, containing a full complement of pairs of chromosomes, are called diploid ("two copies"), since they have two copies of each chromosome; sperm and eggs, which do not carry pairs of chromosomes, instead carrying only one copy of each chromosome, are called haploid ("single copy").
So far, so good.
What does this mean for chromosome 7, and coat color? Well in a dog like Tina or Quentin from last issue, there is no confusion with regard to reproductive cells. Only one kind of sperm or egg -- containing the "b" allele for the Landseer trait or the "B" allele for the black trait -- is produced. But what of Steven or Rona? Such dogs produce a 50:50 mixture of "B" and "b" alleles containing eggs and sperm -- since only one copy or the other of the two copies of chromosome 7 end up in any given egg or sperm cell.
Figure Three sums everything up, again, with
Quentin and Rona. How the dog looks (phenotype); examining chromosome
7 to determine what genes are actually carried, masked or unmasked (genotype);
what kind of sperm or eggs these dogs produce; and thus what kinds of offspring
to expect in a test cross (Punnett Square).
Incidentally, the value of a test cross at this point -- just as with Quentin and Rona in the last column and in this one -- is to establish whether or not the black Newfie is a homozygous black ("BB") or a heterozygous black ("Bb"). This is accomplished by mating the unknown black Newfie with a Landseer (since all Landseers are ONLY "bb" dogs -- why do you think that is so?). If the unknown black is homozygous for this trait, all of the offspring will be black (and, of course, all of the puppies will be "Bb" heterozygous blacks), while if the unknown black is heterozygous for this trait, there will be a 50 -- 50 mix of blacks and Landseers ("Bb" and "bb" genotypes).
Now go back to Zach and Zelda, from the last column. Draw up your own Figure Three, using those dogs instead of Quentin and Rona. C'mon, it is only a very mild homework assignment.
Is everything clearer, now? Relatively speaking, of course.
The problem, of course, is that the above business
takes place with all of the chromosomes, not just chromosome 7, and not
simply with elementary coat color traits like black versus Landseer.
Also, there can be more than two allelic forms of genes. And -- appropriate
to our discussion of coat color in Newfies, some genes can act on other
genes, modifying their "blueprint," and therefore the visible phenotype.
So something as seemingly simple as coat color (black or Landseer) can
be further modified by other genes (brown, gray, etc).
At present, I would like all of you to appreciate the following ideas and nomenclature: haploid, diploid, somatic, germline, allele, mitosis, meiosis, chromosome pairs, heterozygote, homozygote, dominance, recessiveness, and test crosses. Any questions? * * * *
Genetic Literacy, Part V
(Or: The Gene that Wouldn't Die, Long Hidden Traits, Multigenerational Puppy Surprises,
the Value of Madonna-Free Test Matings, and How Your Intrepid Columnist
Briefly Hit the “Fast Forward” Button a Little Early to Prove a Point..)
(c) 1992 Mark Martin
As this column meanders along in a Drunkard's Walk
(remember physics class, and the description of random motion?) approach
to illustrating genetic literacy, I suspect that many readers are asking
the question I always hated when I was a teaching assistant in graduate
“So, what's the point of all this?”
Usually said with a sneer, by a well dressed, self important student from a rich, arrogant family (and yeah, who drove a really cool sports car and had a brainy drop-dead gorgeous girlfriend; do you detect the sharp tang of sour grapes?). Actually, the worst question was, and is: “Do I have to know that for the final?”
So, in this column, I will explain -- rather simplistically, but what else is new in the columns I write?-- what exactly is the point of this series, Genetic Literacy. And yes, you will have to know it for the final exam, so to speak.
I'll make it short and sweet: the main value, for most dog owners, of genetic literacy is the understanding of genetic disease. More specifically, how to recognize and avoid it in potential purchases and breedings.
I have been spending a fair amount of time in this column diddling around with coat color in dogs. The reason is that the Landseer / black coat color trait in Newfoundlands is a relatively simple, easy to understand, white bread kind of Mendelian trait (yes, you're right: coat color can indeed be quite complex, but not at this level, OK?). Though my handling of canine coat color was simplistic, it served an important purpose: to explain simple Mendelian genetics. You know, homozygotes, heterozygotes, alleles, dominance, recessiveness, Punnett Squares, genotypes, phenotypes, environmental effects (phenocopies, remember?) and so on.
Still, none of the simplistic stuff helps the concerned reader with understanding canine genetic disease, in all its protean and complex menace: dwarfism, subaortic heart stenosis, osteochondritis dissecans, hip dysplasia (are there still wonks out there who do not accept the genetic nature of this bane of the giant breeds?), retinal atrophy, hemophilia, entropion, ectropion, autoimmune disorders, and on and on. The reason that I began this column series with such a simple (relatively, anyway) trait as coat color was not only to help illustrate simple concepts in genetics, but to show the root problem in the elimination of genetic diseases in dogs: hidden genes.
To explain what I mean, I have to retreat to what I call the Central Paradox of genetics.
1. Genes must be transmitted from generation to generation with great fidelity and very little error.Yet,
2. Small errors must accumulate in genes at a low rate, or evolution will not occur.If no mistakes occur in the genes, no mutations appear, and simply put: your children will look exactly like you. And very few errors actually do appear in DNA. You see, the DNA contained in chromosomes has near miraculous powers of proofreading itself and eliminating errors, large and small. High levels of errors in the DNA would certainly be lethal to the beastie in question, obviously.
That change, or mutation, must occur in the germ
line tissues (the cells that give rise to sperm and eggs). If it
occurs in nongerm line cells, the soma, then the change from B / b
will never be noticed -- and if the change does not occur in the germline,
it absolutely cannot be transmitted to the next generation, for
So, this is the story of two black Newfoundlands, Kepler and Kassandra. One day, Kepler ate a radioactive cookie (there I go again), and as a result, one of his spermatocytes was changed, such that his normal coat color chromosome pair was changed from B / B into B / b (Figure One). Remember, that change is due to one infinitesimal change in one tiny part of a minuscule chromosome, in one cell that cannot even be seen without a microscope.
Kepler looks just the same, still glossy and black of coat (remember, only one bit of one cell changed ). In any event, Kepler and Kassandra have a shared heated and romantic moment, with Ravel's Bolero playing softly in the back of the kennel. Rather than play the voyeur, let's get down (so to speak) to the cellular level. Remember meiosis? Well, Kassandra's eggs all contain the same single coat color chromosome with the “B” allele (remember that though chromosomes do come in pairs, sperm and eggs can only hold one half of each chromosome pair---haploid to a somatic cell's diploidy). But poor, mutated Kepler no longer only produces “B” allele bearing sperm. He now produces two types of sperm, containing either the “B” or “b” alleles.
In any event, Kassandra brings forth a litter of black, wriggly puppies. They look the same as any other litter of Newfoundland puppies. But there are some differences, because of Kepler's contribution. So let's have a look at Kassandra's puppies (Figure Two):
Notice that half of Kassandra's puppies are genotypically
/ b, just like Kepler. Yet they are all black dogs, phenotypically.
And when those dogs grow up, and are mated with other black dogs
(possessing the B / B allele pair), their litters will be all black
too -- but only phenotypically. Genotypically, those litters will
again be a 50 : 50 mix of B / B and B / b puppies (though
they look identically black, of course). The 50 : 50 genotypic mix
of puppies will happen each and every time a B / b dog is
bred to a B / B dog. Even over many hundreds of generations,
Think about it. That pesky “b” allele which originated in Kepler (due to a random mistake) does not go away. Just as I mentioned earlier, that “b” allele will be as faithfully and accurately copied as the standard “B” allele. And you can also see that genes do not die. Oh, sure, if the B / b half of Kassandra's litter died, there would be no more occurrences of the “b” allele in her progeny (provided Kepler joins the Monks of New Skete in upstate New York).
But if a tragedy does not happen, very early on, the mutant “b” allele will spread widely throughout the black Newfoundland population with time. No one will be the wiser, at first, since B / b and B / B dogs are phenotypically identical: they are both black dogs.
The only way that anyone will ever know that a “new” allele like “b” has crept silently and insidiously into the canine population is because of inbreeding. Suppose that Kepler and Kassandra are big name dog show and conformation ring winners. Why then, every other Newfoundland breeder would want to use Kepler at stud, or use Kassandra's offspring in their own breeding programs. Champions breed champions, don't they?
After a while, especially if Kepler and Kassandra's progeny are also winners, the Newfoundland family tree begins to branch less and less, and starts to resemble a scraggly bush. Therefore, many “lines” of winning Newfoundlands will share strong genetic ties to Kepler and Kassandra. And eventually, two breeders working with such related bloodlines will want to cross their dogs, since both kennels produce such great champions.
So the Top Breeder #1 introduces his star dog, Horatio, to Top Breeder #2's fantastic show bitch, Helena. They have no way to know that both Horatio and Helena, though phenotypically black, are genotypically B / b.
Figure Three shows the surprising (to
the breeders, anyway) results of that breeding: 25% B / B
(homozygous black), 50% B / b (heterozygous black, but “carrying”
the “b” allele), and 25% b / b (homozygous Landseer). Even
in this case, notice that half the litter is still carrying a “hidden”
copy of the “b” allele
So what, you might say. But...what if no judge or show superintendent had ever seen or heard of a Landseer coat color pattern? The b / b dogs would surely be disqualified from the conformation ring, right? Word would soon leak out that “weird dogs” were coming out of Breeder 1 and Breeder 2's supposedly award winning kennels. No more dog food commercials, right? And how often would Horatio be called to stud after producing a litter containing what judges would surely call a genetic fault (remember, I mean no disrespect to Landseer fanciers)?
The result would be Breeder 1 and Breeder 2 blaming one another for the “fault,” when you and I know that both Horatio and Helena carried the “b” allele (it's the only way that a b / b dog can show up in the litter ). Name calling, acrimonious fights, rumors, and so on would quickly ensue.
Is this starting to sound familiar?
Laugh at the coat color example if you will, but by studying family records, scientists have been able to trace the hemophilia that plagued the European royal families in the late nineteenth and early twentieth centuries to Queen Victoria's Prince Consort, Albert...and since his extensive family records revealed absolutely no incidence of hemophilia, the entire genetic mess appears to have resulted from a mutation in the gentleman's, ah... reproductive arsenal, very much as I have described above, in the case of Kepler and Kassandra.
Let's return, for the moment, to our “never before seen” Landseer example. How would breeders eliminate the “b” allele from the Newfoundland population (c'mon, it's only an example)? The problem is simple: it is not possible to tell, at a glance, the difference between B / B and B / b dogs; they are both black. The genotype, after all, is locked inside the DNA, and invisible to the eye.
If one could identify heterozygotes, perhaps by some genetic engineering wizardry carried out on a blood or skin sample, then it would be simple to eliminate the “b” allele and eventually the Landseer trait: just prevent all B / b dogs from breeding. However, we cannot identify the B / b heterozygote directly. What is the answer?
Suppose you have a black “mystery dog,” that may be B / B or B / b (remember, you cannot tell the difference). You want to know if the ebony beast carries the “b” allele (genotypically B / b). So, mate the mystery dog with a known Landseer (genotypically b / b). I won't draw out the Punnett square for you (there's your homework ), but you will get one of two types of litters:
1. All black litter: the mystery dog was genotypically B / B (and the resultant litter is all B / b, of course).or
2. Half black and half Landseer litter: the mystery dog was genotypically B / b (the resultant litter is half B / b and half b / b).
Now, consider this information and relate it back to genetic disease, not coat color. Think about it. The “b” allele spreads around easily, since it is recessive, and a B / B x B / b mating results in 50% B / b dogs The “b” allele can spread quite widely, in only a few generations.
In this column, I have shown how a mutation (the
“b” allele) can silently spread throughout a population with time (because
“b” is recessive to “B”). When related animals (due to the silent
spread of the “b” allele) mix, and two heterozygotes (B / b) carrying
a silent “b” allele are bred, a quarter of their offspring will be homozygous
for the “b” allele. The normally recessive trait will thus be unmasked
and expressed---the Landseer coat color trait in Newfoundlands for our
harmless example. Yet this situation also occurs with some genetic
diseases (say, recessive dwarfism in English spaniels). The only
way to identify a heterozygote (so that only B / B animals are used in
a breeding program) at this time is by test mating an animal under consideration
with a known homozygotic b / b. The phenotypic pattern of
“b” allele inheritance will reveal whether the animal under consideration
is B / B or B / b. Tough choices need to be made, obviously.
Whew We are done. But all of this was relatively simple stuff: a good old familiar Mendelian recessive. Genetic diseases, of course, often come in more complicated hereditary flavors. As I discuss genetics further, I will try to keep the focus on what I consider the central theme of this column series: discussing how to reduce the incidence of genetic diseases in dogs.
[Unfortunately, it is here that the columns end. I hope reproducing these columns by Mark Martin from 1991-92 will help to equip Newfie buyers and breeders with the basic genetic literacy -- to the end that they understand the need to seek, retain, and analyze information about siblings of breeding stock. -mm]