Canine factor VII deficiency: lessons learned in applying methods-based laboratory proficiency testing.

Area of Science:

• Veterinary Genetics
• Canine Hematology
• Molecular Diagnostics

Background:

• Canine inherited factor VII deficiency is a common inherited coagulopathy.
• Genetic testing for this condition can be affected by polymorphisms near the F7 gene.
• Allele dropout, caused by a specific polymorphism, previously led to inaccurate results in Beagles.

Purpose of the Study:

• To identify and address the cause of inaccurate genetic testing for canine factor VII deficiency.
• To improve the reliability of genotyping for the F7 gene mutation in dogs.
• To implement a robust internal proficiency program for veterinary genetic testing.

Main Methods:

• Identified two polymorphisms near the F7 gene mutation.
• Developed two independent genotyping assays with minimally non-overlapping primer pairs.
• Redesigned clinical genetic tests to account for identified polymorphisms.
• Re-examined canine samples using the improved testing methods.

Main Results:

• A polymorphism near the F7 gene was found to cause allele dropout in Beagles.
• The redesigned assays successfully identified correct genotypes in all re-examined dogs.
• The internal proficiency program enhanced testing accuracy.

Conclusions:

• The study successfully identified and mitigated a source of error in canine factor VII deficiency genetic testing.
• Implementation of dual, independent genotyping methods ensures higher accuracy for F7 mutation testing.
• Improved testing protocols enhance diagnostic reliability for inherited coagulopathies in dogs.