Association of early onset myasthenia gravis in Newfoundland dogs with the canine major histocompatibility complex class I

作者：Wolf Zena; Vernau Karen^*; Safra Noa; Shelton G Diane; King Jason; Owen Joseph; Weich Kalie; Bannasch Danika

来源：Neuromuscular Disorders, 2017, 27(5): 409-416.

DOI：10.1016/j.nmd.2017.01.020

• Canine
• Myasthenia gravis
• Major histocompatibility complex (MHC)
• Dog leukocyte antigen (DLA)
• Autoimmune diseases
• Human leukocyte antigen (HLA)

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. MTIC 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.

• 出版日期2017-5