title: High frequency of a single nucleotide substitution (c.-6-180T>G) of the canine MDR1/ABCB1 gene associated with phenobarbital-resistant idiopathic epilepsy in Border Collie dogs.
abstract: A single nucleotide substitution (c.-6-180T>G) associated with resistance to phenobarbital therapy has been found in the canine MDR1/ABCB1 gene in Border Collies with idiopathic epilepsy. In the present study, a PCR-restriction fragment length polymorphism assay was developed for genotyping this mutation, and a genotyping survey was carried out in a population of 472 Border Collies in Japan to determine the current allele frequency. The survey demonstrated the frequencies of the T/T wild type, T/G heterozygote, and G/G mutant homozygote to be 60.0%, 30.3%, and 9.8%, respectively, indicating that the frequency of the mutant G allele is extremely high (24.9%) in Border Collies. The results suggest that this high mutation frequency of the mutation is likely to cause a high prevalence of phenobarbital-resistant epilepsy in Border Collies.
authors.affiliation: Laboratory of Clinical Pathology, Department of Veterinary Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Mizukami
authors.forename: Akira
authors.initials: A
authors.lastname: Yabuki
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Chang
authors.forename: Mohammad Mejbah
authors.initials: MM
authors.lastname: Uddin
authors.forename: Mohammad Mahbubur
authors.initials: MM
authors.lastname: Rahman
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kushida
authors.forename: Moeko
authors.initials: M
authors.lastname: Kohyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamato
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy / Q000235:genetics*; D004285:Dogs; D004351:Drug Resistance; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D010634:Phenobarbital / Q000494:pharmacology* / Q000627:therapeutic use; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000927:Anticonvulsants; D010634:Phenobarbital