title: Linkage of hyperkalaemic periodic paralysis in quarter horses to the horse adult skeletal muscle sodium channel gene.
abstract: A genetic disease observed in certain Quarter horses is hyperkalaemic periodic paralysis (HYPP). This disease causes attacks of paralysis which can be induced by ingestion of potassium. Recent studies have shown that HYPP in humans is due to single base changes within the adult skeletal muscle sodium channel gene. A large Quarter horse pedigree segregating dominant HYPP was studied to determine if mutations of the sodium channel gene are similarly responsible for HYPP in horses. We used cross-species, PCR-mediated, cDNA cloning and sequencing of the horse adult skeletal muscle sodium channel alpha-subunit gene to identify a polymorphism, and then used this polymorphism to see if the horse sodium channel gene was genetically linked to HYPP in horses. The sodium channel gene was indeed found to be tightly linked to HYPP (LOD = 2.7, theta = 0). Our results suggest that HYPP in horses involves the same gene as the clinically similar human disease, and indicates that these are homologous disorders. The future identification of the specific sodium channel mutation causing HYPP in Quarter horses will permit the development of accurate molecular diagnostics of this condition, as has been recently shown for humans.
authors.affiliation: Department of Molecular Genetics & Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261.
authors.forename: J A
authors.initials: JA
authors.lastname: Rudolph
authors.forename: S J
authors.initials: SJ
authors.lastname: Spier
authors.forename: G
authors.initials: G
authors.lastname: Byrns
authors.forename: E P
authors.initials: EP
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001483:Base Sequence; D004262:DNA Restriction Enzymes / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005838:Genotype; D006734:Horse Diseases / Q000235:genetics*; D006736:Horses; D006947:Hyperkalemia / Q000235:genetics / Q000662:veterinary*; D008297:Male; D008969:Molecular Sequence Data; D009132:Muscles; D009154:Mutation / Q000235:genetics; D010245:Paralyses, Familial Periodic / Q000097:blood / Q000235:genetics / Q000662:veterinary*; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D015222:Sodium Channels; D004262:DNA Restriction Enzymes