Leonbergers In the 21 st Century A Genetics Primer

Transcription

1 Leonbergers In the 21 st 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 Page 1 of 6

2 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 Page 2 of 6

3 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 Page 3 of 6

4 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 Page 4 of 6

5 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. Page 5 of 6

6 References Bell, Jerold S. Facing Breed Related Diseases as a Vet--Practical and Ethical Aspects Lindblad-Toh, et al (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438(7069): 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 Page 6 of 6