Narcolepsy in Labrador Retrievers is a sleeping disorder characterized by daytime sleepiness, fragmented sleep patterns, and sudden transient episodes of muscle weakness or paralysis triggered by play or food. This test detects a causal variant specific to Labrador Retrievers.
Phenotype: Narcolepsy is a sleeping disorder commonly characterized by daytime sleepiness, fragmented sleep patterns, and sudden, transient episodes of muscle weakness or paralysis triggered by play or food. Signs appear suddenly, recovery from them is spontaneous, and there is usually no progression in severity of signs after the dog’s first year.
Mode of Inheritance:Autosomal recessive
Alleles: N = Normal/Unaffected, NAL = Labrador Retriever narcolepsy variant
Breeds appropriate for testing: Labrador Retriever, Labradoodle
Explanation of Results:
Dogs with N/N genotype will not have this inherited narcolepsy and will not transmit this narcolepsy variant to their offspring.
Dogs with N/NAL genotype will not have this inherited narcolepsy, but are carriers. They will transmit this narcolepsy variant to 50% of their offspring. Matings between two carriers are expected to produce 25% narcolepsy-affected puppies.
Dogs with NAL/NAL genotype will develop this inherited narcolepsy and will transmit this narcolepsy variant to all of their offspring.
Narcolepsy is a disabling neurological disorder that has been identified in several dog breeds, including the Labrador Retriever. This disease affects the brain’s ability to control sleep-wake cycles. It is characterized by daytime sleepiness, erratic sleep patterns, fast transition to rapid eye movement (REM) sleep, and sleep paralysis, but the most striking symptom is cataplexy – sudden loss of muscle tone and collapse without loss of consciousness – which can be triggered by strong positive emotional stimulus such as play or food. Usually, signs appear between 4 weeks and 6 months of age and severity increases until animals are approximately 1 year old, when progression stops.
Narcolepsy in Labrador Retrievers is caused by a single nucleotide change (or SNP) in the Hypocretin Receptor 2(HCRTR2)gene that causes exon-skipping and produces an abnormal protein. The G to A substitution in the 5’ splice site causes the deletion of exon 6 which, in turn, produces a truncated HCRTR2 protein (330 amino acids instead of the normal 444 amino acids) that cannot properly regulate sleep-wake cycles in affected dogs. The mode of inheritance for this disease is autosomal recessive, which means that males and females are equally affected and that two copies of the mutation are needed to cause narcolepsy. Screening of a random set of Labrador Retrievers at the VGL determined that the HCRTR2 disease allele is rare in this breed, with frequency less than 1%.
Testing for narcolepsy in Labrador Retrievers assists clinicians with diagnosis of narcolepsy and helps breeders identify carriers among breeding stock and select appropriate mates to reduce the risk of producing affected offspring. In order to avoid the possibility of producing affected puppies, matings between known carriers are not recommended.
Note: This test does not detect the mutation that causes narcolepsy in Dobermans or Dachshunds.
Normal. Dog does not carry the Labrador narcolepsy associated variant.
Carrier. Dog has one copy of the Labrador narcolepsy associated variant.
Affected. Dog has two copies of the Labrador narcolepsy variant and will develop symptoms of narcolepsy.
Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P. J., Nishino, S., & Mignot, E. (1999). The sleep disorder canine narcolepsy is caused by a mutation in the Hypocretin (Orexin) Receptor 2 gene. Cell, 98(3), 365-376. doi: 10.1016/s0092-8674(00)81965-0
Hungs, M., Fan, J., Lin, L., Lin, X., Grigoriadis, D., Maki, R. A., & Mignot, E. (2001). Identification and Functional Analysis of Mutations in the Hypocretin (Orexin) genes of narcoleptic canines. Genome Research, 11(4), 531-539. doi: 10.1101/gr.gr-1610r