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

Grant Status: Closed

Grant Amount: $12,927
Dr. David Sargan,; University of Cambridge
February 1, 2007 - July 31, 2008
Sponsor(s): Golden Retriever Foundation
Breed(s): Tibetan Terrier
Research Program Area: Prevention

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 FH, Johnson GS, Taylor JF, Giuliano E, Katz Ml, Sanders DN, Schnabel RD, Mckay SD, Khan S, Gharahkhani P, O'leary CA, Pettitt L, Forman OP, Boursnell M, Mclaughlin B, Ahonen S, Lohi H, Hernandez-Merino E, Gould DJ, Sargan D and Mellersh CS (2010

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