April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Whole-Genome Association Study Identifies the Canine Cone-Rod Dystrophy 2 Locus
Author Affiliations & Notes
  • G. M. Acland
    James A Baker Institute,
    Cornell University, Ithaca, New York
  • J. G. Mezey
    Cornell University, Ithaca, New York
  • A. R. Boyko
    Cornell University, Ithaca, New York
  • C. Gao
    Cornell University, Ithaca, New York
  • W. Wang
    Cornell University, Ithaca, New York
  • C. D. Bustamante
    Cornell University, Ithaca, New York
  • G. D. Aguirre
    School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
  • O. Goldstein
    Cornell University, Ithaca, New York
  • Footnotes
    Commercial Relationships  G.M. Acland, Optigen LLC, I; Optigen LLC, C; J.G. Mezey, None; A.R. Boyko, None; C. Gao, None; W. Wang, None; C.D. Bustamante, None; G.D. Aguirre, Optigen LLC, I; Optigen LLC, C; O. Goldstein, None.
  • Footnotes
    Support  NIH Grants EY006855, -13132,-17549, GM082910; Foundation Fighting Blindness; Morris Animal Foundation; Van Sloun Fund
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4046. doi:
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      G. M. Acland, J. G. Mezey, A. R. Boyko, C. Gao, W. Wang, C. D. Bustamante, G. D. Aguirre, O. Goldstein; Whole-Genome Association Study Identifies the Canine Cone-Rod Dystrophy 2 Locus. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4046.

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      © ARVO (1962-2015); The Authors (2016-present)

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Introduction: : Canine Cone-Rod dystrophy 2 (crd2) is an early onset, hereditary retinal degeneration identified in the American Pit Bull Terrier dog breed. It is characterized by initial severe day-blindness, progressing to total blindness by 1 year. A colony segregating the disease has been established.

Purpose: : To identify the locus responsible for Cone-Rod Dystrophy 2 by whole-genome association study (WGAS).

Methods: : DNA was extracted from 14 crd2-affected cases and 13 unaffected related controls using standard protocols. A WGAS was undertaken using the Affymetrix Version 2, Canine SNP chip following the standard protocol. Genotypes were called using "MAGIC" algorithm and tested for association using Fisher’s Exact test. A Bonferroni correction for multiple tests set the significance threshold at -Log10(p) > 6.39.

Results: : Two potentially associated loci were identified, although neither passed the significance threshold. The lower of the 2 peaks yielded a signal of 4.17. Linkage analysis to crd2 in pedigrees showed no co-segregation, suggesting a false positive hit. The second locus on CFA33 included 5 SNPs with a signal of 6.13, approaching the Bonferroni threshold. Linkage analysis showed significant co-segregation. Haplotype analysis identified a 2.7 Mb homozygosity block- the presumed crd2 Linkage Disequilibrium interval. Candidate genes evaluation is now in progress.

Conclusions: : Carefully selected case and control groups for a WGAS, with as few as 13-14 dogs per group, successfully identified a region on CFA33 that potentially harbors the crd2 gene. Combined WGAS and Linkage analysis can exclude false positives and confirm true positive association hits even if genome wide significance thresholds are not achieved.

Keywords: retinal degenerations: hereditary • genetics • linkage analysis 

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