Transcript Test
Test • Similar format to other tests • Today's lecture included • Lecture should be included on web site by this pm • Thursdays lab in Kildee pavilion Genetics of Disease • Modes of Inheritance –Dominant –Recessive –Complex Genetics of Disease • Modes of Inheritance –Dominant • Late onset diseases –Recessive –Complex Dog and Cat Genetic Diseases • Mechanism of genetic disease – Mutations • Random and spontaneous – Mutations become consentrated in the population over many generations • Two mechanisms • Founder effect • Popular sire or dam effect Founder Effect • Often a missused term • A disease allele is concentrated in a small or new population (foundation population) at a higher relative frequency from the originating population • Original population, 1/1,000 • New popluation 1/10 • Example: Angus cattle in Australia and New Zealand and alpha-mannosidosis • Portuguese Water Dogs (15 animals founded the population) • Initial development of breeds was likely foundation event Popular Sire or Dam Effect • Dog and cat fancy breeding often involves heavy use of popular sires or dams • This effectively concentrates desirable alleles in the population • If the heavily used animal is carrying a mutant allele, it will also increase that allele in the population Founder and Popular Effect • Founder effect is often a missused term • Most common recessive genetic diseases are the result of: – Popular sire or dam effect – Popular sire or dam effect and founder effect Pedigree Example Founder effect compounded by popular sire/dam effect How old is a mutation • Difficult to say • If it is a common allele, one assumes not a recent mutation • Serious or biomedically important diseases receive scrutiny not inline with being clinically common conditions – Example is mucopolysaccharidosis type VII in German shepherd dogs – First seen in mixed-breed dog – 25 years later published case in German shepherd dog Age of Mutations in a Population • Mutant alleles seen in different, but closely related breeds of dogs • Examples – West Highland white and Cairn terriers • Krabbe disease (globoid cell luekodystrophy) – German shorthair and wirehair pointers • Von Willebrand disease – Assuming no mixing of breeds, mutations occurred before breeds were formed in mid-late 19th century Recessive Genetic Disease in Dogs and Cats • Dozens of genetic disease in dogs and cats for which genetic tests exist • Involve serious inherited recessive diseases of various body systems – Vision – Lysosomal Storage Diseases – Hematological Disorders Commercial DNA Based Testing • • • • Testing for diseases Testing for traits Testing for parentage University based, single tests – Usually developer of tests • University based, multiple tests and services • Commercial laboratories, University spin-offs • Commercial laboratories, usually little to no development • Price $75-$150 • Who you gonna call? Vet Gen Coat Color Tests • The B and b alleles of the dog – Three mutations in Tyrosinase Related Protein-1 (TRP1) involved in the chocolate coat color in “bb” Labrador retrievers (and dogs of many other breeds). • The E and e alleles of the dog – One mutation in the the Melanocortin-1 Receptor (MC1R) gene that causes the the yellow coat color in “ee” dogs. Tests Available for 33 different Breed Tests Lysosomal Storage Disease in Veterinary Patients • Documented in virtually every major veterinary species except the horse • Usually severe disease seen in the young animal • At least 21 different forms identified in over two dozen breeds of dogs and cats • Mixed breed dogs and cats also documented • Molecular defect known in at least 20 cases • Documentation of certain breeds affected with more than one form of lysosomal storage disease (English Springer Spaniel (2), and Siamese Cat (3)) Breed Specific Tests Airdale Terrier English Cocker Spaniels Miniature Poodle American Cocker Spaniels English Pointer Miniature Schnauzer Australian Cattle Dogs English Setter Newfoundland Australian Shepherd English Springer Spaniel Nova Scotia Duck Tolling Retrievers Basenji Field Spaniel Basset Hound Flat-coated Retriever Pembroke Welsh Corgi Bedlington Terrier German Short-haired Pointer Poodles (all varieties) Bernese Mountain Dog German Wire-haired Pointer Portuguese Water Dog Briard Golden Retriever Samoyeds Brittany Spaniel Great Dane Schipperke Bull Terrier Greyhound Scottish Terrier Bullmastiffs Irish Setters Shetland Sheepdog Cairn Terrier Irish Red & White Setters Shih Tzu Cardigan Welsh Corgi Kerry Blue Terrier Chesapeake Bay Retrievers Labrador Retriever Curly-Coated Retriever Dachshunds Dalmatian Doberman Pinscher Large Munsterlander Lhasa Apso Manchester Terrier Mastiffs Miniature Pinschers Papillon Siberian Huskies Sloughis Toy Poodles West Highland White Terrier Wheaten Terrier Whippet Wire-haired Pointing Griffon Canine Scientific Investigation (CSI) • DNA Sample collection and submission • Blood – Requires a veterinarian to collect and ship – What kind of blood sample? • Cytology brushes – Can be collected by owner DNA Testing Results • Carrier versus Normal versus Affected • Allows carriers to be used safely • Should carrier animals be continued to breed? • How common are carrier animals in some of these disorders? DNA Tests and Breeding • Carrier animals can be safely bred, and in some cases, the genetic health of the breed may depend on using such animals • Carrier rates can reach over 20% in some breeds and some diseases.