title: Association of early onset myasthenia gravis in Newfoundland dogs with the canine major histocompatibility complex class I.
abstract: Acquired Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder whose development in humans has been associated with the Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA). There is a form of early onset MG (EOMG) in Newfoundland dogs that mimics the clinical presentation in humans and appears to have familial inheritance. Genotyping of three classical Dog Leukocyte Antigen (DLA) class II genes, DLA-DRB1, DLA-DQA1 and DLA-DQB1, in 16 Newfoundlands with EOMG and 46 unaffected Newfoundlands, identified DLA-DQB1 *00301 (p-value = 0.0051 OR: 7.41) as a risk locus for the development of EOMG in this breed. In order to further investigate the extent of the association to the entire MHC region, 208 additional SNPs were genotyped in two phases. Both a risk locus for EOMG to the DLA class I (chr12: 458483-506460) and a protective locus for EOMG susceptibility that extends outside of the DLA class I (chr12: 89701-475348) were identified. Four additional dog breeds with an elevated risk for the development of MG were SNP genotyped, but no shared or significant associations were found. MHC involvement in canine MG disease manifestation overlaps with loci identified in human studies and highlights the value of dogs as a model for genetic studies of naturally occurring diseases.
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
authors.forename: Zena
authors.initials: Z
authors.lastname: Wolf
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA. Electronic address: kmvernau@ucdavis.edu.
authors.forename: Karen
authors.initials: K
authors.lastname: Vernau
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
authors.forename: Noa
authors.initials: N
authors.lastname: Safra
authors.affiliation: Department of Pathology School of Medicine, University of California, San Diego, San Diego, CA, USA.
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.affiliation: William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: King
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Owen
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
authors.forename: Kalie
authors.initials: K
authors.lastname: Weich
authors.affiliation: Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
authors.forename: Danika
authors.initials: D
authors.lastname: Bannasch
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D005805:Genes, MHC Class I; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D008297:Male; D009157:Myasthenia Gravis / Q000235:genetics / Q000662:veterinary*; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity
keywords: Autoimmune diseases; Canine; Dog leukocyte antigen (DLA); Human leukocyte antigen (HLA); Major histocompatibility complex (MHC); Myasthenia gravis