Related Experiment Videos
The molecular defect underlying canine fucosidosis
B J Skelly1, D R Sargan, M E Herrtage
1Department of Clinical Veterinary Medicine, University of Cambridge, UK.
Journal of Medical Genetics
|April 1, 1996
Summary
Fucosidosis, a genetic lysosomal storage disease, is caused by a deficiency in alpha-L-fucosidase. A 14-base pair deletion in the canine fucosidase gene causes a frameshift mutation, leading to disease in English springer spaniels.
Area of Science:
- Genetics
- Biochemistry
- Veterinary Medicine
Background:
- Fucosidosis is a rare, recessively inherited lysosomal storage disease affecting humans and English springer spaniel dogs.
- It stems from a deficiency of the enzyme alpha-L-fucosidase, crucial for glycoprotein catabolism.
Purpose of the Study:
- To identify the genetic mutation responsible for fucosidosis in English springer spaniels.
- To characterize the canine fucosidase gene and its associated mutations.
Main Methods:
- Cloning and sequencing of the canine fucosidase gene.
- Single-strand conformation polymorphism (SSCP) based mutation analysis of the coding region using exonic and intronic primers.
- Polymerase chain reaction (PCR) based genomic cloning of DNA from affected animals.
Main Results:
- The canine fucosidase gene spans 12 kb and comprises eight exons.
- A 14-base pair deletion was identified at the 3' end of exon 1 in affected dogs, also present at the start of intron 1.
- This deletion results in a frameshift, leading to 25 novel codons and premature stop codons in exon 2.
Conclusions:
- A specific 14-base pair deletion in the canine fucosidase gene is the causative mutation for fucosidosis in English springer spaniels.
- This mutation leads to a non-functional alpha-L-fucosidase enzyme due to frameshift and premature termination of translation.