title: Detection of a genetic mutation for myotonia congenita among Miniature Schnauzers and identification of a common carrier ancestor.
abstract: OBJECTIVE
  To develop a molecular genetic test to detect the mutant skeletal muscle chloride channel (CIC-1) allele that causes myotonia congenita in Miniature Schnauzers and to analyze the relationship of affected and carrier dogs.
  
  
  METHODS
  372 Miniature Schnauzers from the United States, Canada, Australia, and Europe that were tested between March 2000 and October 2001.
  
  
  METHODS
  The sequence surrounding the mutation in the CIC-1 allele was amplified by use of a unique pair of primers. Polymerase chain reaction (PCR) products were digested with the restriction enzyme Hpy CH4 III and separated on a 6% polyacrylamide gel. Pedigrees from all available carrier and affected dogs were analyzed, and a composite pedigree was established.
  
  
  RESULTS
  Enzyme digestion of PCR products of the normal CIC-1 allele resulted in 3 fragments of 175, 135, and 30 bp, whereas PCR products of the mutant allele resulted in fragments of only 175 and 165 bp. Of the 372 Miniature Schnauzers, 292 (78.5%) were normal, 76 (20.4%) were carriers, and 4 (1.1%) were affected (myotonic) dogs. Frequency of the mutant allele was 0.113. Pedigree analysis revealed that a popular sire, documented to be a carrier, was a common ancestor of all carriers and affected dogs.
  
  
  CONCLUSIONS
  A PCR-based enzyme digestion DNA test was developed. The mutant allele for this disease is frequent in Miniature Schnauzers that are related to a common carrier ancestor. Breeding dogs should be tested by this specific DNA test to help limit the spread of this deleterious mutation.
authors.affiliation: Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6010, USA.
authors.forename: Dilip P
authors.initials: DP
authors.lastname: Bhalerao
authors.forename: Yashoda
authors.initials: Y
authors.lastname: Rajpurohit
authors.forename: Charles H
authors.initials: CH
authors.lastname: Vite
authors.forename: Urs
authors.initials: U
authors.lastname: Giger
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000145:classification* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D008297:Male; D009154:Mutation / Q000235:genetics*; D009224:Myotonia Congenita / Q000235:genetics* / Q000662:veterinary*; D010375:Pedigree
chemical_list: C086321:CLC-1 channel; D018118:Chloride Channels