00881-A: Identifying the Mutation Causing Lens Luxation in the Tibetan Terrier

Grant Status: Closed

Grant Amount: $12,927
David Sargan, MA, PhD; University of Cambridge
February 1, 2007 - July 31, 2008

Sponsor(s): Golden Retriever Foundation

Breed(s): Tibetan Terrier
Research Program Area: Ophthalmology
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Project Summary

PURPOSE. To identify the genetic cause of isolated canine ectopia lentis, a wellcharacterized veterinary disease commonly referred to as primary lens luxation (PLL). METHODS. Genome-wide association analysis and fine mapping by homozygosity were used to identify the chromosomal segment harboring the PLL locus. The resequencing of a regional candidate gene was used to discover a mutation in a splice donor site predicted to cause exon skipping. Exon skipping was confirmed by reverse transcription-polymerase chain reaction amplification of RNA isolated from PLL-affected eyes and from skin fibroblast cultures from PLL-affected dogs. A TaqMan allelic discrimination assay was used to genotype individual dogs at the splice donor site mutation. RESULTS. The PLL locus was mapped to a 664 kb region of canine chromosome 3 containing regional candidate gene ADAMTS17. Resequencing ADAMTS17 revealed a GT-to- AT splice-donor-site mutation at the 5' end of intron 10. The predicted exon 10 skipping and resultant frame shift was confirmed with RNA derived from PLL-affected dogs. The ADAMTS17 mutation was significantly associated with clinical PLL in three different dog breeds. CONCLUSION. A truncating mutation in canine ADAMTS17 causes PLL, a well characterized veterinary disease.


Farias, F. H. G., Johnson, G. S., Taylor, J. F., Giuliano, E., Katz, M. L., Sanders, D. N., … Mellersh, C. (2010). An ADAMTS17 Splice Donor Site Mutation in Dogs with Primary Lens Luxation. Investigative Ophthalmology & Visual Science, 51(9), 4716–4721. https://doi.org/10.1167/iovs.09-5142

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