A novel risk locus on canine chromosome 18 is identified for congenital laryngeal paralysis in Alaskan sled dogs – Presented by Heather J. Huson

Congenital laryngeal paralysis (CLP) is a hereditary disease, causing loss of movement of the arytenoid cartilage and focal folds in the larynx during inspiration. This reduced function causes varying degrees of respiratory distress which can negatively affect a dog’s physical ability and become life-threatening.  The congenital form, commonly diagnosed within 1 year of age has been described in multiple breeds but is less common than the acquired form, often an age-related disease.  For Alaskan sled dogs (ASD), bred specifically for endurance, CLP can drastically affect their growth and performance.  To this end, 20 CLP affected, and 198 unaffected ASD were used in a genome-wide association study to explore the genetic regulation of CLP in ASD with the intention of developing a genetic test. 120,296 single-nucleotide polymorphisms spanning the canine genome highlighted a novel risk locus on chromosome 18 (Bonferroni corrected p<4.5×107) and suggestive associations (p<8.3×106) on chromosomes 4, 23, and 31.  Focusing on chromosome 18, the markers of highest association identified a 3.2KB region of the genome comprising the EXT2 (exostosin glycosyltransferase 2) gene.  Nearby regions of linkage highlighted by significantly associated markers identified the tumor protein TP53I11 (p53 inducible protein 11), TSPAN18 (tetraspanin 18), and SHANK3 (SH3 and multiple ankyrin repeat domains) genes.  Mutations in EXT2 and TP53I11 have been associated with skeletal and muscular developmental disorders and tumors, while mutations in TSPAN18 and SHANK3 have been implicated in neurological disorders. Further investigations are ongoing to identify the most plausible candidate gene and causative mutations of CLP in ASD.