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Transcript
Genetics Article 1 for LL
6/14/11 6:38 PM
Leonbergers In the 21st Century – A Genetics Primer
Author’s Note: Ready or not, the dog world is changing fast, and Leonberger folks have the
option of standing still, getting out of the way, or continuing to run with the alphas.
Throughout our history we have always been a bit ahead of the curve. Essig created the
Leonberger fifteen years before the birth of the dog fancy and a quarter century before
Germany became a nation. The International Leonberger Union was among the first of the
multi-nation breed alliances. The East and West German Leonberger clubs reunited a few
days before the Berlin Wall was formally breached. And, in 1995, the LCA was one of the
first breed clubs in the world to conduct a nationwide health survey. We had an unheard of
56% of the 800 LCA-registered dogs responding (the average for parent clubs is 8%). This
July, with the announcement of the LPN1 genetic marker test, the door has been thrown
open to our breed’s genome just as it is being thrown open all over the world for every
purebred dog. Within the next few decades every purebred dog’s genotype will be as visible
as his or her phenotype. This is already beginning to alter breed standards, the way judges
will choose winners and the way we, our children and our grandchildren will choose our
next canine companions. So, ready or not, it’s time to learn.
“Toto, We’re not in Kansas anymore.”
The world of dog breeding and dog shows is changing so rapidly that it
might sometimes feel like we’ve been swept up in a Midwest tornado and
dropped into a new world where words and phrases like autosome,
heterozygous, nucleotide, SNP (spoken as snip), or microsatellite are beginning
to be tossed around as often as taking group, typey, well-angulated, line-bred,
or short croup. Advances in science are propelling the dog world, as we know
it and as it has been known for 150 years, to change into something quite new.
Since the Victorians created the dog fancy, breeders, judges, and the
person looking for a fashionable dog or the cutest pup with the waggliest tail
were basing their judgments on the criteria set down in rigidly formatted
written standards. Current breed standards describe only how a quality
specimen of a breed is supposed to look and behave. Health and longevity
have never been significant elements of standards, and judges can almost
never determine either element during brief observation in the show ring.
Breeders have been forced to rely on luck, test breedings, experience and
some classical genetic principles resting on the centuries-old notion that “like
begets like’.
While devouring Darwin’s ideas about progress through natural and
artificial selection, the dog fancy conveniently ignored his warning that, in
selecting for any single trait or peculiarity, other structures and functions will
automatically be altered too. As early as 1868, Darwin was pointing out to
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the British dog-owning public that breed-associated defects were present in
purebred dogs. But what couldn’t been seen could easily be ignored,
especially when the trophies and fame went to the show ring winners.
Revealing The Genotype
The breakthrough scientific descriptions of Charles Darwin and Gregor
Mendel emerged about the same time that modern day breeds were being
created. These ideas provided dog breeders with important fundamental tools
that are basis of what we call classical genetics. The studies that were
conducted on observable traits like coat color, bone structure and canine
behavior are still valid and important today.
During the same 150 years that the dog fancy was methodically spreading
across nations, creating its own culture and spawning major industries, the
science of genetics was exploding into several disciplines, among them
molecular genetics, behavioral genetics, population genetics, quantitative
genetics, and epigenetics. All of these disciplines focus on ideas that
increasingly bring clarity to our Leos’ genotypes and will help determine their
future.
Twentieth-century dog breeders understood the nature of chromosomes and
quite a bit about the significance of dominant and recessive genes and their
alleles. Breed phenotypes became more refined, approaching and even
sometimes surpassing, the ideals laid down in the written standards. Some
breeders got so carried away in their quest to excel in the beauty points
described in their breeds’ standards that their dogs’ basic functions like
breathing, walking, and giving birth became impaired. Fortunately, the
Leonberger escaped that tendency.
However, even though classical genetic principles are well understood by
today’s breeders and a good portion of the dog-owning public, genotypes still
remain shrouded in mystery. And, what isn’t easily seen can be ignored or
wildly misunderstood. It easy to deny, or explain away, case by case, the
diseases that are becoming ever more apparent in the closed gene pools of
purebred dogs.
DNA and the Leonberger Genome
Scientists started studying DNA about the time of the first dog shows in
Europe in the mid-nineteenth century. But, it’s complicated stuff and it wasn’t
until just over fifty years ago that they figured out that it was the key to life—all
of life. You, your Leonbergers, fleas, viruses, liver treats, and foxtails are all
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composed of trillions of cells that dutifully carry out instructions known as
genes that are packaged in chromosomes, each composed of a long, skinny
molecule of DNA tightly coiled around some proteins living in a special part of
the cell called its nucleus.
When James Watson and Francis Crick took the work of Rosalind Franklin
(without her knowledge), and in 1953 pulled back the curtain on the
workings of the fundamental stuff of all life, it was a moment that changed
everything. Whole new areas of studies have opened and the keys to
unlocking the mysteries of traits, inheritance, reproduction, aging and disease
are available. They may be like needles in a haystack, but the haystack has
been found.
In December 2005, Dr. Kirsten Lindblad-Toh, a good friend of the
Leonberger, and a dozen other researchers published a paper in the journal,
Nature, announcing that they had found that handful of needles and straw in
the haystack linked to all dogs’ DNA. It took scientists from universities and
research institutes all over the world working together to compile a complete
sequence of 2.4 billion chemical letters that make up the canine genome—
the complete manual of instructions for making and maintaining a dog (see
illustration and explanation on page _____). In addition, they created a map
of 2.5 million individual differences that serve as signposts which can be
used to locate specific genes that govern physical and behavioral traits as
well as disease.
The genome sequence and the corresponding map made it possible for
scientists, like our friends at the University of Minnesota, to locate those
pieces of DNA responsible for the bad instructions that cause one form of
Leonberger Polyneuropathy. Other scientists are currently searching for faulty
instructions in Leonbergers that give rise to canine cancers and single
descended testicles.
Genetics Is Not Just for Breeders Anymore
This summer, Jerold S. Bell, DVM, Tufts University professor and frequent
consultant to the AKC’s Canine Health Foundation, addressed the Congress
of the World Small Animal Veterinary Association, and stated unequivocally
that it is not only the responsibility of breeders, but equally of breed
organizations/parent clubs, and the general public to stay abreast of canine
genetic tests and their results. According to Dr. Bell, if two animals are
purposefully bred, then the breed-specific genetic testing for each parent is
ethically required. Bell stresses that breed clubs must conduct regular breed
health surveys and promote and fund tests to be used by breeders. As the
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economic driver, every consumer who gets a puppy can and must require full
disclosure on the genetic health of their new family member. It is the
veterinarian’s role to counsel and facilitate ethical and responsible behavior
on the part of all the players.
Starting With DNA
You don’t need to understand the entire workings of the internal combustion
engine to drive a car. And you don’t have to get a degree in genetics to breed
beautiful dogs, administer a breed club, or live happily with a healthy
Leonberger. But, you need enough information to make wise acquisition
decisions, keep things running smoothly, know when something is wrong, and
go about getting things right or as right as possible. So, it’s a good idea to take
time to add a few new words to your vocabulary and to grasp a few of the
essentials.
Since DNA is the fundamental stuff of life, it’s an ideal place to start. DNA,
or deoxyribonucleic acid, is the molecule that, in concert with certain proteins,
make up each of the chromosomes that reside in the control center or nucleus
of every cell in your Leonberger’s body. This weak acid naturally forms the
long, twisted ladder shape called a double helix that has become one of the
most familiar symbols in our modern day world.
Amazingly, DNA is composed of only four chemicals called nucleotides.
Each nucleotide has three parts: a sugar molecule, a phosphate molecule and a
structure called a nitrogenous base. The nitrogenous base is the part that caries
the genetic information, so the words nucleotide and base are often used
interchangeably. In your reading about canine genetic tests you will frequently
come across the term, base pairs.
Base pairs form the rungs of the DNA ladder. The four bases are adenine,
cytosine, guanine and thymine. They are referred to as Base A, Base T, Base C
and Base G. Each ladder rung is made up of only two bases (thus, a pair). Base
C is always paired with Base G and Base A is always paired with Base T.
The magic of DNA is that it is the only molecule found in living things that
can make an exact copy of itself. The two strands of the DNA double helix,
unzip themselves and each makes a template. Free unattached nucleotides
floating around in the cell line up in formation, attach themselves to the
templates and form new identical double strands.
The bases of a strand of DNA use only a four-letter alphabet to create code
words. The words written in genetic code consist of three letters in a row such
as GGC or ATG. There are 64 of these different words. A sequence of these
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words makes up a gene just as the words you are reading make up a sentence.
Genes are, therefore, simply sentences made up of words built from only four
letters. As in most fundamental scientific truths, reality is simultaneously
astonishingly simple and elegantly complex.
The fly in the ointment is that there are no spaces between the words. And,
to complicate matters only 5% of the long strand of DNA is made up of genes.
The other 95% are long strings of base pairs in seemingly random patterns. At
the moment these are called “junk DNA.” But it is clear these sequences are
important too, we just haven’t figured out the how and why yet. If you have
ever done a word search, you were hunting for words a bit like like molecular
geneticists hunt for genes, but they are working with a couple of billion letters.
DNA is the Code, Proteins Crack the Code and Do The Work
Almost everything in your Leonberger’s body (and yours too) is either made
by or composed of proteins. Some proteins cause chemical reactions while
others actually form structures like fur, muscles and scent detectors. All of
these proteins are made up of building blocks called amino acids. There are
only twenty different kinds of these building blocks. They are joined together
according to a set of coded instructions. Yep, you guessed it. The coded
instructions are the genes stored in the DNA.
When a gene is “read,” the code describes which amino acids to use and in
what order to join them together. There are thousands of body proteins and
each is made up of a sequence of amino acids. Remember that 95% of the long
strings of base pairs still seem random to scientists. So it is vital that some of the
three letter codes serve as traffic lights. They tell the cells where to start reading
the code and where to stop when the substance it is making is complete. All of
this miracle of life is happening right before your eyes every time you reach out
your DNA-and-amino-acid-filled hand to pat the DNA-and-amino-acid-filled
forehead of your amazing Leo.
It’s when there is an error in the code or a mistake in following DNA
instructions that things can go terribly wrong. The tools are now available to
find errors in a Leonberger’s genotype. Scientists are working hard every day to
isolate the genes that would cause harm if they are passed on to baby Leos. So,
take a deep breath, participate in the upcoming 2010 Leonberger Health
Survey, send blood and DNA swabs for researchers to use, donate money to the
Leonberger Health Foundation when you can, and cherish every minute you
spend with your healthy Leo.
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References
Bell, Jerold S. Facing Breed Related Diseases as a Vet--Practical and Ethical Aspects
http://www.vin.com/Proceedings/Proceedings.plx?CID=WSAVA2010&PID=56153&O=Generic
Lindblad-Toh, et al (2005) Genome sequence, comparative analysis and haplotype structure of the
domestic dog. Nature 438(7069):803-819.
This article is based on excerpts from Caroline Bliss-Isberg’s forthcoming book, The Complete
Leonberger, An Authoritative Guide to the Lion King of Dog Breeds © Caroline Bliss-Isberg 2010
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