Closing The Gap ~ The Time Path

Improving the conformation, health and temperament of purebred dogs should be the goal of every breeder. What makes this goal reachable began when the studbook for breeds closed. The result was the establishment of specific breeds. By definition closing the stud book means that the diversity of the genes for a breed would be restricted to those already present. Thus when a stud book closes no new genes are allowed into the breeds that were not already present in the gene pool. The exception is the occurrence of a few infrequent mutations. By closing a gene pool the pedigrees of each breed became dependable and reliable as a tool for improving breed type, health and temperament. Further refinements occurred as breeders began to use breed standards as their guide for breeding and selection. The result produced a large number (N=170) of desirable breeds with verifiable ancestries. Over time these closely monitored populations have become especially suitable for the study of diseases. Most of the major advances have occurred during the past two decades. With the advancement of DNA tests more improvements became possible at a faster pace. Other notable advancements included those in the area of digital radiographs, laboratory tests, nutrition and better breeding methods. Today, breeders can use these protocols to breed by direction rather than by chance.

When the canine genome sequencing project was first undertaken the American Kennel Club, Canine Health Foundation (AKC/CHF) became one of its largest non-profit supporters. Once it was completed the canine genome joined four other completed sequences, including one for the human and another for the chimpanzee. Many benefits were quickly realized. The breakthrough discovery on Neuronal Ceroid Lipofuscinosis (Tibetan Terriers) led to landmark stem cell replacement therapy in a California boy who was suffering with a disorder called Batten Disease. Other useful advancements quickly followed. For example, a test was developed for copper toxicosis (CT) in Bedlington Terriers where 25% are affected, 50% are carriers and only 25% are clear (Bell). Other was discoveries included a test for juvenile cataracts in Boston Terriers along with the mechanism involved in the transmission of the tick-borne disease, Rocky Mountain Spotted Fever (Brewer). Genetic markers for illnesses in Basenjis, Standard Poodles and English Cocker Spaniels followed. These technological advancements demonstrate what can be accomplished when breeders, clubs and research efforts are combined.

The key to this kind of success involves cooperation and sufficient funding. Perhaps the best example was the collaborative effort between the AKC/CHF and the Orthopedic Foundation for Animals (OFA) which resulted in the development of the Canine Health Information Center (CHIC) (www.caninehealthinfo.org). CHIC is an online registry that works with parent clubs to establish a panel of testable disorders for specific breeds. The CHIC concept is that dogs achieve a CHIC certification by completing the health-checks identified by their breed club. Passing each health test is not a requirement for certification. CHIC is about being health conscious, not about being faultless. For those not ready to share in an open database CHIC offers a way to protect the privacy of their information. CHIC enters all test information into their database. Breeders who chose to restrict their test results participate in the aggregate because summary data is useful for research and statistical reporting.

CHIC functions not only as a tool for breeders and their clubs but as a resource for health information that can be shared in various ways. In this respect, every breeder can participate even if they are only willing to share limited amounts of information. Restricted data has value because it can be used for general searches about diseases and traits. This is often useful for research and the calculation of statistical averages. For example, summary data is useful to breeders who wish to compare their results to their breed’s average.

Since its inception the AKC/CHF has funded more than 340 studies. Many of the top ten diseases found in purebred dogs are being studied at 74 veterinary schools and research institutions worldwide including those located in Argentina, Great Britain, France, Germany, Australia, and the Netherlands. Because of the many new methods and technological breakthroughs that have occurred there are more than 60 DNA tests now available for screening breeding stock.

THE TIME PATH

One of the major obstacles in bringing new DNA tests forward is called the time-path. This is the amount of time and effort required to identify a problem, characterize it, call it by its proper name, and secure funding. If the researcher is successful and discovers a solution, a protocol is developed for use by veterinarians and breeders. Unfortunately, the time-path is often longer than most expect. For example, once a project has been indentified and funded, blood samples and pedigrees must be collected. If the researcher is successful and a marker found, the next step is to make the information available in an easy to use and understandable manner. The time-path for the total process can be as short as a few years or as long as a decade. Each time a new test or new method is developed a new learning curve begins. Veterinarians and breeders must learn what laboratories can administer the test, how the results can be used and interpreted and what mechanism is available to identity and mange the carriers. With this kind of information and technology the genes that took years to collect can be saved while diseases and disorders can be controlled and eliminated.

With DNA technology and new breeding protocols the problems of the breeder can be addressed more directly. In the past the popular approach was to simply eliminate all of the carriers and affected dogs from a breeding program. Unfortunately, this approach quickly affected the diversity of a breed’s gene pool. Others took a different approach and conducted test-matings to identify carriers, affected and normals. This did not prove to be a desirable method because the undesirable genes are either present or not and test breedings often produced affected dogs that had to be carefully placed or euthanized. More recently better methods have become available that can reduce many of the problems of the past. For example, DNA testing can be used to eliminate problems because it allows breeders to manage carriers while saving the genes needed to maintain breed type and temperament. The screening of breeding stock followed by the selection of quality offspring offers a significant improvement over test-matings.

It has been well established that DNA tests will help breeders decrease the frequency of defective genes. If no test is available carriers can be carefully bred. The approach recommended is to breed carriers to those that appear normal when evaluated. The assumption is that the breeder will follow-up on the offspring produced. Using this approach breeders can select normal offspring for future breedings. This is a slower and less certain approach and it will not eliminate all of the carriers but it will reduce their frequency.

Because of the increased awareness of diagnostic tests better decisions can be made with positive results. The following tests and laboratories that administer tests for genetic disorders and some conformation traits are listed.

CANINE GENETIC TESTS - 2008

DISORDER	BREED	TEST TYPE	TEST ORG
Canine Leukocyte Adhesion Deficiency (CLAD)	Irish Red & White Setter Irish Setter	Direct	Optigen
Cataract, Juvenile (Early onset Hereditary Cataract – EHD)	Boston Terrier French Bulldog Staffordshire Bull Terrier	Direct	Optigen
Ceroid lipofuscinosis	Border Collie	Direct	Optigen
Ceroid lipofuscinosis	American Bulldog Dachshund England Setter	Direct	U Missouri
Coat Color & Nose Color Variations	Australian Shepherd Border Collie Brittany Belgian Shepherd Belgian Tervuren Cardigan Welsh Corgi Collie (Rough, Smooth) Cocker Spaniel Curly-Coated Retriever Belgian Malinois Dachshund Dalmatian Doberman Pinscher English Cocker Spaniel English Setter English Springer Spaniel Field Spaniel Flat-coated Retriever French Bulldog German Shepherd Dog German Long Haired Pointer German Wirehaired Pointer Great Dane Greyhound Groenendael Labrador Retriever Laekenois Large Munsteriander Lowchen Newfoundland Pointer Pomeranian Poodle Portuguese Water Dog Pudelpointer Shetland Sheepdog Staffordshire Bull Terrier Whippet Wirehaired Pointing Griffon	Direct	HealthGene
Coat Color Gene Variations	Alaskan Klee Kai American Cocker Spaniel Australian Cattle Dog Border Collie Curly Coated Retriever Dalmatian Doberman Pinscher English Cocker Spaniel English Springer Spaniel Flat Coated Retriever Gordon Setter Labrador Retriever Newfoundland Pointer Poodle Schipperke Scottish Terrier Stumpy Tail Cattle Dog	Direct
Coat Length (FGF 5)	Weimeraner	Direct	Animal Health Trust
Cobalamin Malabsorption (Methylmalonic Aciduria)	Australian Shepherd Giant Schnauzer	Direct	PennGen
Collie Eye Anomaly (Choroidal Hypoplasia)	Australian Shepherd Border Collie Lancashire Heeler Nova Scotia Duck Tolling Retriever Rough Coated Collie Shetland Sheepdog Smooth Coated Collie Whippet Longhair	Direct	Optigen
Cobalamin Malabsorption (Methylmalonic Aciduria)	Beagle Border Collie DSH Shar Pei	Phenotypic	Penn Gen
Cone (Retinal) Degeneration	German Shorthaired pointer	Direct	Optigen
Congenital Hopothyroidism With Goiter (CHG)	Rat Terrier Toy Fox Terrier	Direct	Michigan State U. Fyfe Lab PennGen
Congenital Stationary Night Blindness (RPE65-CSNB)	Briard	Direct	Optigen Animal Health Trust
Cystinuria	Newfoundland Labrador Retriever	Direct	Optigen (Newf only) PennGen VetGen (Newf only)
Degenerative Myelopathy (DM)	German Shepherd Dog (Flash test) Boxer (RAPD) Pembroke Welsh Corgi (RAPD) Rhodesian Ridgeback (RAPD)	Direct Susceptibility loci)	U-Florida Neuro Service
Factor VII Deficiency	Alaskan Klee Kai Beagle Scottish Deerhound	Direct	PennGen
Factor IX Deficiency	Kerry Blue Terrier	Direct	PennGen
Fanconi Syndrome	Basenji	Linked Marker	U-Missouri
Fanconi Syndrome	Basenji Norwegian Elkhound	Phenotypic	PennGen
Fucosidosis	English Springer Spaniel	Direct	PennGen Animal Health Trust
Glanzmann’s Thrombasthenia (Type I)	Great Pyrenees Otterhound	Direct	Auburn U – Boudreaux Lab
Globoid cell leukodystrophy	Cairn Terrier West Highland White Terrier	Direct	Jefferson Medical College
Glycogenosis (GSD) Type IIIa	Curly Coated Retriever	Direct	Mich. State U Fyfe Lab
Glycogenosis (GSD) Type IV	Norwegian Forest Cat	Direct	PennGen
GM1-Gangliosidosis	Portuguese Water Dog	Direct	NYU, Neurogenetics Lab
Hypertrophic Cardiomyopathy	Maine Coon Cat Ragdoll	Direct	Washington State U., Meurs Lab
Ivermectin Sensitivity (MDR-1)	Australian Shepherd Collie Old English Sheepdog Shetland Sheepdog	Direct	Washington State U., Pharm Lab
L-2-HGA (L-2-hydroxyglutaric aciduria)	Staffordshire Bull Terrier	Direct	Animal Health Trust
Mannosidosis	DSH Persian	Direct	PennGen
Merle Gene (SILV)	Australian Shepherds Beauceron Shepherd Border Collie Cardian Welsh Corgi Catahoula Leopard Dog Chihuahua Cocker Spaniel Collie Dachshund Great Danes Norwegian Hound Pitt Bull Pomeranian Pyrenean Shepherd Shetland Sheepdogs	Direct	GenMark
Mucolipidosis II (I-Cell Disease)	DSH	Direct	PennGen
Mucopolysaccaharidosis (MPS)	DSH German Shepherd Dog Miniature Pinscher Miniature Schnauzer Schipperke Siamese	Direct	PennGen
Muscular Myopathy (Centronuculear Myopathy)	Labrador Retriever	Direct	Alfort School of Vet Medicine, France
Myotonia Congenita	Miniature Schnauzer	Direct	Optigen PennGen
Narcolepsy	Dachshund Doberman Pinscher Labrador Retriever	Direct	Optigen
Neonatal Encephalopathy	Standard Poodle	Direct	U Missouri
Neophropathy (Hereditary N., Familial N.)	English Cocker Spaniel	Direct	Optigen
Phosphofructokinase\| Deficiency (PFK)	American Cocker Spaniel English Springer Spaniel	Direct	Optigen PennGen VetGen Animal Health Trust
Polycystic Kidney Disease (PKD)	American Shorthair Himalayan Persian Scottish Fold	Direct	UC-Davis – Lyons Lab. Animal Health Trust
Primary Hyperparathyroidism	Keeshond	Linkage	Cornell – Goldstein Lab.
Progressive Retinal Atrophy (cord1)	Dachshund, Miniature Longhaired English Springer Spaniel	Direct	Animal Health Trust U Missouri
Progressive Retinal Atrophy Dominant	Bullmastiff English Mastiff	Direct	Optigen
Progressive Retinal Atrophy (prcd)	American Cocker Spaniel American Eskimo Dog Australian Cattle Dog Chesapeake Bay Retriever Chinese Crested Cockapoo English Cocker Spaniel Entelbucher Mt. Dog Finnish Lapphund Golden Retriever Kuvasz Labradoodle Labrador Retriever Lapponian Herder Nova Scotia Duck TrollingRetriever Poodle (miniature, toy) Portuguese Water Dog Spanish Water Dog Stumpy Tail Cattle Dog Swedish Lapphund	Direct	Optigen
Progressive Retinal Atrophy (rcd1)	Irish Red & White Setter Irish Setter	Direct	Optigen Animal Health Trust
Progressive Retinal Atrophy (rcd3)	Cardigan Welsh Corgi	Direct	Mich. State U. - Peterson-Jones Lab. Optigen VetGen
Progressive Retinal Atrophy (rcd1a	Sloughi	Direct	VetGen (Irish Setter)
Progressive Retinal Atrophy – Type A	Miniature Schnauzer	Direct	Optigen
Progressive Retinal Atrophy – X-Linked	Samoyed Siberian Husky	Direct	Optigen
Pyruvate Dehydrogenase Phosphatase Deficiency (PDH or PDP 1)	Clumber Spaniel Sussex Spaniel	Direct	U Missouri Animal Health Trust
Pyruvate Kinase Deficiency (PK)	Abyssinian American Eskimo Dog Basenji Beagle Cairn Terrier Chihuahua Dachshund DSH Somali West highland White Terrier	Direct	Optigen (Basenji) PennGen (All) VetGen (Basenji) Animal Health Trust (Westies)
Renal Dysplasia	Lhasa Apso Shih Tzu Soft Coated Wheaten Terrier	Linkage	VetGen
Retinal Dysplasia – Canine Multi-focal retinopathy (CMR)	Bullmastiff Coton de Tulear Dogue de Bordeaux Great Pyrenees Mastiff (English & French)	Direct	Optigen
Severe Dysplasia – Canine Multi-focal Retinopahty (CMR)	Bullmastiff Coton de Tulear Dogue de Bordeaux Great Pyrenees Mastiff (English & French)	Direct	PennGen
Severe Muscular Atrophy	Maine Coon Cat	Direct	Michigan State U – Fyfe Lab.
Thrombopathia	Bassett Hound Landseer Sptiz	Direct	Auburn U – Boudreaux Lab.
Trapped Neutrophil Syndrome (TNS)	Border Collie	Linkage	U. New South Wales
Von Willibrand’s Diesase	Bernese Mt Dog Doberman Pinscher Drentsche Patrijshound German Pinscher Kerry Blue Terrier Manchester Terrier Papillion Pembroke Welsh Corgi Poodle Scottish Terrier Shetland Sheepdog	Direct	VetGen
Von Willibrand’s Diesase	Irish Red & White Setter	Direct	Animal Health Trust

CONTACT LABORATORY SOURCES:

Alfort School of Veterinary Medicine: France, http://www.labradorcnm.com
Animal Health Trust: (England): http://www.aht.org.uk/sci_disc_genetics_dna.html#canine
Auburn University – Boudreaux Lab: http://www.vetmed.auburn.edu/index.pl/Boudreaux_mk   (334) 844 2692
Cornell – Goldstein Lab.: http://www.vet.cornell.edu/labgoldstein/ (607) 253 4480
Cornell Univ. Comparative Coagulation Lab. http://www.diaglab.vet.cornell.edu/coag/test/hemopwh.asp ( 607) 275 0622
GenMark: http://www.genmarkag.com/home_companion.php   (877) 766 3446
Health Gene: www.hearthgene.com   (877) 371 1551
Jefferson Medical College: David.wenger@mail.tju.edu
Michigan State University – Peterson-Jones Lab: http://www.cardigancorgis.com/PraPressRelease.aspx (517) 353 3278
New York University Neurogenetics lab: http://pwdca.org/GM1app.html (212) 263 2943
Optigen: www.optigen.com (607) 257 0301
PennGen: www.vet.upenn.edu/penngen   (215) 898 8894
UC Davis – Lyons Lab: http://www.vgl.ucdavis.edu/service/catPKD.html (530) 752 2211
U Missouri – Johnson Lab: http://www.caninegeneticsdiseases.net/ (573) 884 3712
U New South Wales- Wilton Lab: a.wilton@unsw.edu.au
U Florida – Neuro Service: http://www.neuro.vetmeded.ufl.edu/dm_flash_test_web/index.html (352) 392 4700 x 4700
VetGen: www.vetgen.com (800) 483 8436
Washington State U – Meurs Lab: http://www.vetmed.wsu.edu.edu/deptsVCGL/ (509) 335 6038
Washington State U – Pham Lab: http://www.vetmed.wsu.edu.edu/annonements/invermectin/ownerinfo.asp (509) 335 3745

REFERENCES:

Bell, Jerold, “The Healthy Dog”, American Kennel Club Gazette, New York, New York, February, 2001.
Bell, Jerold, “The Effects of Genetic Testing”, American Kennel Club Gazette, New York, New York, June, 2001.
Brewer, George, “Canine Molecular Genetic Diseases”, Tufts’ Canine and Feline Breeding and Genetics Conference,
Sturbridge, MA., September 30 – October 1, 2005.

ABOUT THE AUTHOR
Carmen L Battaglia holds a Ph.D. and Masters Degree from Florida State University. He is an AKC judge, researcher and writer; he has been a leader in promoting better ways to breed dogs. An author of many articles and several books, he is also a popular guest on TV and radio talk shows including several appearances on Animal Planet. His seminars on breeding dogs, selecting sires and choosing puppies have been well-received by breed clubs. Those interested in learning more about his articles and seminars should visit the website: h ttp://www.breedingbetterdogs.com