title: Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders.
abstract: BACKGROUND
  The growing number of identified genetic disease risk variants across dog breeds challenges the current state-of-the-art of population screening, veterinary molecular diagnostics, and genetic counseling. Multiplex screening of such variants is now technologically feasible, but its practical potential as a supportive tool for canine breeding, disease diagnostics, pet care, and genetics research is still unexplored.
  
  
  RESULTS
  To demonstrate the utility of comprehensive genetic panel screening, we tested nearly 7000 dogs representing around 230 breeds for 93 disease-associated variants using a custom-designed genotyping microarray (the MyDogDNA® panel test). In addition to known breed disease-associated mutations, we discovered 15 risk variants in a total of 34 breeds in which their presence was previously undocumented. We followed up on seven of these genetic findings to demonstrate their clinical relevance. We report additional breeds harboring variants causing factor VII deficiency, hyperuricosuria, lens luxation, von Willebrand's disease, multifocal retinopathy, multidrug resistance, and rod-cone dysplasia. Moreover, we provide plausible molecular explanations for chondrodysplasia in the Chinook, cerebellar ataxia in the Norrbottenspitz, and familiar nephropathy in the Welsh Springer Spaniel.
  
  
  CONCLUSIONS
  These practical examples illustrate how genetic panel screening represents a comprehensive, efficient and powerful diagnostic and research discovery tool with a range of applications in veterinary care, disease research, and breeding. We conclude that several known disease alleles are more widespread across different breeds than previously recognized. However, careful follow up studies of any unexpected discoveries are essential to establish genotype-phenotype correlations, as is readiness to provide genetic counseling on their implications for the dog and its breed.
authors.affiliation: Genoscoper Laboratories Oy, Helsinki, Finland.
authors.forename: Jonas
authors.initials: J
authors.lastname: Donner
authors.affiliation: Research Programs Unit-Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kaukonen
authors.affiliation: Genoscoper Laboratories Oy, Helsinki, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Anderson
authors.affiliation: Genoscoper Laboratories Oy, Helsinki, Finland.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Möller
authors.affiliation: Research Programs Unit-Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Kaisa
authors.initials: K
authors.lastname: Kyöstilä
authors.affiliation: Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Sankari
authors.affiliation: Research Programs Unit-Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Hytönen
authors.affiliation: Section of Medical Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Urs
authors.initials: U
authors.lastname: Giger
authors.affiliation: Genoscoper Laboratories Oy, Helsinki, Finland.|Research Programs Unit-Molecular Neurology, University of Helsinki, Helsinki, Finland.|Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.|Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
mesh_terms: D000818:Animals; D024141:Collagen Type IV / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D004392:Dwarfism / Q000235:genetics / Q000662:veterinary; D005167:Factor VII / Q000235:genetics; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D039001:Integrin alpha Chains / Q000235:genetics; D009154:Mutation; D013045:Species Specificity; D014527:Uric Acid / Q000652:urine; D052878:Urolithiasis / Q000235:genetics / Q000662:veterinary
chemical_list: D024141:Collagen Type IV; D039001:Integrin alpha Chains; D014527:Uric Acid; D005167:Factor VII