title: Genetic heterogeneity of day blindness in Alaskan Malamutes.
abstract: Day blindness is a progressive and specific degeneration of cone photoreceptors in the retina of young dogs. This disorder has been associated with a breed-specific non-synonymous substitution in exon 6 of the cyclic nucleotide gated channel beta3 (CNGB3) gene in German Shorthaired Pointer dogs and a genomic deletion removing the entire gene in Alaskan Malamute dogs from the USA. To further investigate this disorder, we characterized CNGB3 in a three-generation pedigree of Alaskan Malamute dogs from Australia segregating for day blindness. Fifteen of the dogs showed clinical signs of day blindness. Four of these were definitively diagnosed by standardized electroretinography. Polymerase chain reaction amplification of exon 6 of CNGB3 was attempted, and as expected, amplification was successful in the 18 unaffected or carrier dogs. However, a non-mutated exon 6 was also amplified and sequenced in six of the 15 affected dogs. On sequencing each exon and exon/intron boundary in two such affected individuals and two unaffected individuals, three exonic substitutions and 12 intronic changes were noted. These sequence variations in affected individuals were also present in one or both unaffected dogs and so appear to have no obvious effect on the protein's function. Hence, day blindness shows genetic heterogeneity within the Alaskan Malamute population of Australia, a result that is somewhat unexpected given the relatively small effective population size of this breed.
authors.affiliation: School of Veterinary Science, The University of Queensland, St Lucia, Qld, Australia. j.seddon1@uq.edu.au
authors.forename: J M
authors.initials: JM
authors.lastname: Seddon
authors.forename: E C G M
authors.initials: EC
authors.lastname: Hampson
authors.forename: R I E
authors.initials: RI
authors.lastname: Smith
authors.forename: I P
authors.initials: IP
authors.lastname: Hughes
mesh_terms: D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D017353:Gene Deletion; D018740:Genetic Heterogeneity; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology; D010375:Pedigree; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D014786:Vision Disorders / Q000235:genetics / Q000662:veterinary*
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels