Suspected autosomal recessive primary ciliary dyskinesia in a colony of Labrador Retriever guide dogs – Presented by Katy Evans

Over a 23 year period, 11 litters were born in a guide dog breeding program in which one or more puppies developed characteristic respiratory clinical signs around 2 weeks of age.  These included nasal discharge, chronic rhinitis and recurrent upper respiratory tract infections which sometimes progressed to bronchopneumonia.  Mycoplasma cynos was often found on culture, but no primary diagnosis was determined until early 2023 by electron microscopy.  Nasal biopsy samples from one affected dog revealed changes suggestive of primary ciliary dyskinesia.  In-house pedigree analysis revealed a likely autosomal recessive inheritance pattern, tracing back to one common ancestor.  Genome-wide association studies of 8 cases and 20 case-related control dogs revealed a single significantly associated region on canine chromosome 2.  This region encompasses the SPAG6 (sperm-associated antigen 6) gene which has been suggested to play a role in ciliary dyskinesia in mouse knockout studies as well as being proposed as a mechanism in humans.   A ‘risk haplotype’ of strongly associated single nucleotide polymorphisms (SNPs) was also identified.  All the cases were homozygous for the risk haplotype.  This enabled more accurate identification of carriers in our breeding program.  Identification of carriers based on pedigree analysis, then risk haplotype, has allowed successful avoidance of producing more affected puppies.  Whole genome sequencing of several known cases, parents of cases, unaffected littermates and unaffected unrelated dogs is currently underway to determine a causative mutation.  We are hopeful that this may have been completed by June 2025.  This presentation will discuss how, through partnership with research collaborators at Cornell University, we were able to very quickly stop producing affected puppies once it had been recognized as an inherited condition.  It will be of particular interest to any organization breeding Labrador Retrievers.  We have temporarily paused sharing Labrador/cross germplasm, until the genetic investigation is complete.

Coming soon.