Genome Wide Association Study with Imputed Whole Genome Sequence Data Identifies a 431 kb Risk Haplotype on CFA18 for Congenital Laryngeal Paralysis in Alaskan Sled Dogs.

Congenital laryngeal paralysis (CLP) is an inherited disorder that affects the ability of the dog to exercise and precludes it from functioning as a working sled dog. Though CLP is known to occur in Alaskan sled dogs (ASDs) since 1986, the genetic mutation underlying the disease has not been reported. Using a genome-wide association study (GWAS), we identified a 708 kb region on CFA 18 harboring 226 SNPs to be significantly associated with CLP. The significant SNPs explained 47.06% of the heritability of CLP. We narrowed the region to 431 kb through autozygosity mapping and found 18 of the 20 cases to be homozygous for the risk haplotype. Whole genome sequencing of two cases and a control ASD, and comparison with the genome of 657 dogs from various breeds, confirmed the homozygous status of the risk haplotype to be unique to the CLP cases. Most of the dogs that were homozygous for the risk allele had blue eyes. Gene annotation and a gene-based association study showed that the risk haplotype encompasses genes implicated in developmental and neurodegenerative disorders. Pathway analysis showed enrichment of glycoproteins and glycosaminoglycans biosynthesis, which play a key role in repairing damaged nerves. In conclusion, our results suggest an important role for the identified candidate region in CLP.

Congenital laryngeal paralysis in Alaskan Huskies: 25 cases (2009-2014).

OBJECTIVE To characterize congenital laryngeal paralysis (CLP) in Alaskan Huskies. DESIGN Prospective case series. ANIMALS 25 Alaskan Huskies with CLP. PROCEDURES Data were collected for each dog regarding signalment; history; results of physical, orthopedic, neurologic, and laryngeal examinations; esophagraphic findings; treatments; histologic findings; and outcomes. RESULTS Severely affected dogs were profoundly dyspneic at birth or collapsed after brief exercise; less affected dogs reportedly tired easily or overheated with minimal exercise. Mean age at initial onset of clinical signs was 6.4 months. Blue eyes, white facial markings, and oral mucosal tags or tissue bands were noted in 23 (92%), 19 (76%), and 13 (52%) dogs. Neurologic examination revealed signs of mononeuropathy of the recurrent laryngeal nerve but not of polyneuropathy. Histologic examination revealed neurogenic atrophy of the cricoarytenoideus dorsalis muscle but no polyneuropathy. Eight (32%) dogs underwent unilateral cricoarytenoid lateralization, resulting in substantial clinical improvement, including ability to compete in sled dog races. Without surgery, 4 (16%) dogs died of asphyxiation, 10 (40%) had spontaneous improvement of clinical signs (but insufficient improvement to race), and 3 (12%) remained affected. Results of pedigree analysis suggested an autosomal recessive mode of CLP inheritance, with variable penetrance. CONCLUSIONS AND CLINICAL RELEVANCE CLP in the evaluated Alaskan Huskies involved mononeuropathy of the recurrent laryngeal nerves, without polyneuropathy. Most affected dogs had blue eyes, white facial markings, and oral mucosal tags or tissue bands. Given the apparent genetic component to CLP in this breed, we recommend that dogs with these features be prevented from breeding.

Evaluation of plasma inflammatory cytokine concentrations in racing sled dogs.

In human athletes significant changes in cytokine concentrations secondary to exercise have been observed. This prospective study evaluated the effect of a multi-day stage sled dog race on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). Samples from 20 dogs were harvested prior to and on days 2 and 8 of an 8-day race. Exercise resulted in significantly decreased TNF-α and IL-8 as well as increases of MCP-1, IL-6, and IL-10 concentrations (P-value between 0.01 and < 0.0001 for all parameters). The proportion of values for IL-2 that were below the detection limit increased from 40% on day 0 to 75% on day 2 and decreased on day 8 to 40% (P = 0.04). Racing sled dogs show cytokine-concentration changes that are different from those in humans.

Évaluation des concentrations plasmatiques de cytokines inflammatoires chez des chiens de traîneau de course. Chez les athlètes humains, des changements importants des concentrations de cytokines secondaires à l'exercice ont été observés. Cette étude prospective a évalué l'effet d'une course de chiens de traîneau par étapes de plusieurs jours sur les concentrations plasmatiques des protéines-1 chimio-attractives des monocytes (MCP-1), du facteur-alpha nécrosant des tumeurs (TNF-α), d'interleukine-2 (IL-2), d'interleukine-6 (IL-6), d'interleukine-8 (IL-8) et d'interleukine-10 (IL-10). Des échantillons ont été prélevés sur 20 chiens avant la course et aux jours 2 et 8 d'une course de 8 jours. L'exercice a produit des valeurs significativement réduites de TNF-α et d'IL-8 ainsi qu'une hausse des concentrations de MCP-1, d'IL-6 et d'IL-10 (la valeur-P entre 0,01 et < 0,0001 pour tous les paramètres). La proportion des valeurs pour IL-2 qui étaient inférieures au seuil de détection a augmenté de 40 % le jour 0 à 75 % le jour 2 et a baissé le jour 8 à 40 % (P = 0,04). Les chiens de traîneau de course montrent des changements de la concentration des cytokines qui sont différents de ceux observés chez les humains.(Traduit par Isabelle Vallières).