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O. Goldstein, J. G. Mezey, A. R. Boyko, C. Gao, W. Wang, C. D. Bustamante, G. D. Aguirre, G. M. Acland; Cone- Rod Dystrophy 3 Whole- Genome Association Study Identifies a Locus on Canine Chromosome 16. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1657.
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Canine cone- rod dystrophy 3 (crd3) is an adult onset hereditary disease recognized in the Glen of Imaal Terrier dog breed. The disease is characterized by dysfunction and degeneration of cone photoreceptors preceding that of rods, and progresses eventually to complete blindness. The mode of inheritance has not previously been conclusively established.
To identify the mode of inheritance and the locus responsible for canine crd3 in the Glen of Imaal Terrier breed by whole- genome association study (WGAS).
DNA was extracted from 21 crd3 - affected dogs (cases) and 22 unaffected (controls) using standard protocols. Samples were genotyped using the Affymetrix Version 2, Canine SNP chip following the standard Affymetrix GeneChip® Mapping 250K Sty Assay protocol. Genotypes were called using the "MAGIC" algorithm and tested for association with the disease phenotype using Fisher’s Exact test, and a Bonferroni-corrected significance threshold set at -Log10(p) ≥ 6.39.
WGAS identified one locus on chromosome 16 with significant association to crd3 . The region extended over 6 Mb and included 31 SNPs that exceeded the Bonferroni corrected significance threshold (-Log10(p) range = 6.39 - 10.09). Haplotype analysis reduced the minimal Linkage Disequilibrium to a 2.7 Mb interval and suggests a recessive mode of inheritance. Candidate genes within this interval are now being evaluated.
crd3 is a simple mendelian disease with an autosomal recessive mode of inheritance. WGAS using carefully selected cases and controls, with about 20 dogs per group, identified a region on canine chromosome 16 that potentially harbors the crd3 gene and mutation.
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