Document Type
Journal Article
Date of this Version
10-2010
Publication Source
Molecular Genetics and Genomics
Volume
284
Issue
4
Start Page
243
Last Page
250
DOI
10.1007/s00438-010-0560-5
Abstract
Over 200 mutations in the retina specific member of the ATP-binding cassette transporter superfamily (ABCA4) have been associated with a diverse group of human retinal diseases. The disease mechanisms, and genotype–phenotype associations, nonetheless, remain elusive in many cases. As orthologous genes are commonly mutated in canine models of human blinding disorders, canine ABCA4 appears to be an ideal candidate gene to identify and study sequence changes in dogs affected by various forms of inherited retinal degeneration. However, the size of the gene and lack of haplotype assignment significantly limit targeted association and/or linkage approaches. This study assessed the naturally observed sequence diversity of ABCA4 in the dog, identifying 80% of novel variations. While none of the observed polymorphisms have been associated with blinding disorders to date, breed and potentially disease specific haplotypes have been identified. Moreover, a tag SNP map of 17 (15) markers has been established that accurately predicts common ABCA4 haplotypes (frequency > 5%) explaining >85% (>80%) of the observed genetic diversity and will considerably advance future studies. Our sequence analysis of the complete canine ABCA4 coding region will clearly provide a baseline and tools for future association studies and comparative genomics to further delineate the role of ABCA4 in canine blinding disorders.
Copyright/Permission Statement
The final publication is available at www.springerlink.com
Keywords
ABCA4, haplotype structure, genetic variation, progressive retinal atrophy, canine
Recommended Citation
Zangerl, B., Lindauer, S. J., Acland, G. M., & Aguirre, G. D. (2010). Identification of Genetic Variation and Haplotype Structure of the Canine ABCA4 Gene for Retinal Disease Association Studies. Molecular Genetics and Genomics, 284 (4), 243-250. http://dx.doi.org/10.1007/s00438-010-0560-5
Included in
Animal Diseases Commons, Disease Modeling Commons, Eye Diseases Commons, Medical Genetics Commons, Ophthalmology Commons, Veterinary Medicine Commons
Date Posted: 06 May 2015
This document has been peer reviewed.