Potential modifying loci associated with primary lens luxation, pedal hyperkeratosis, and ocular phenotypes in miniature bull terriers

Gharahkhani, Puya, O' Leary, Caroline A., Duffy, David L. and Kyaw-Tanner, Myat (2015) Potential modifying loci associated with primary lens luxation, pedal hyperkeratosis, and ocular phenotypes in miniature bull terriers. Investigative Ophthalmology and Visual Science, 56 13: 8288-8296. doi:10.1167/iovs.15-18074


Author Gharahkhani, Puya
O' Leary, Caroline A.
Duffy, David L.
Kyaw-Tanner, Myat
Title Potential modifying loci associated with primary lens luxation, pedal hyperkeratosis, and ocular phenotypes in miniature bull terriers
Journal name Investigative Ophthalmology and Visual Science   Check publisher's open access policy
ISSN 1552-5783
Publication date 2015-12-01
Year available 2015
Sub-type Article (original research)
DOI 10.1167/iovs.15-18074
Open Access Status Not yet assessed
Volume 56
Issue 13
Start page 8288
End page 8296
Total pages 9
Place of publication Rockville, MD, United States
Publisher Association for Research in Vision and Ophthalmology
Collection year 2016
Language eng
Formatted abstract
Purpose: Primary lens luxation (PLL) in dogs is an inherited disease in which the lens is displaced from its normal position. A truncating mutation in the ADAMTS17 orthologue on CFA03 is reported to cause PLL in several breeds, mostly terriers. However, the complex inheritance pattern of PLL in miniature bull terriers (MBTs) suggests that other loci may have a modifying effect on the ADAMTS17 mutation. This study aimed to detect such loci increasing risk of PLL in Australian MBTs.

Methods:
More than 170,000 single-nucleotide polymorphisms (SNPs) across the canine genome were genotyped in 23 PLL-affected and 73 normal Australian MBTs, and association between the PLL phenotype and the genetic markers was investigated by using general mixed effects Cox model survival analysis.

Results:
The highest association peaks, other than that associated with the ADAMTS17 mutation (P = 2.2e-05), were SNP BICF2G630420272 located at 62.2 Mb on chromosome 15 (P = 7.8e-05) and the region between 30 Mb and 32.5 Mb on chromosome 1 (P = 9.3e-05). Joint analysis showed that the PLL-associated allele of the BICF2G630420272 SNP increased risk of PLL in the presence of the ADAMTS17 mutation (P = 8.117e-04). Candidate genes in the two regions of interest included CPE on chromosome 15 and CTGF on chromosome 1. The ADAMTS17 mutation was also associated with abnormal foot and nail shapes, pedal hyperkeratosis, and persistent pupillary membranes.

Conclusions: Two loci with potentially enhancing effects on the ADAMTS17 mutation were associated with PLL in Australian MBTs. Association of the ADAMTS17 mutation with possible pedal skeletal abnormalities in MBTs supports PLL in this breed and Weill-Marchesani syndrome-like disease in humans as being homologous diseases.
Keyword ADAMTS17
Miniature bull terriers
Modifying loci
Pedal hyperkeratosis
Primary lens luxation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Veterinary Science Publications
 
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