IQCB1 and PDE6B mutations cause similar early onset retinal degenerations in two closely related terrier dog breeds. Academic Article Article uri icon

Overview

MeSH

  • Animals
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Dogs
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Male
  • Mutation
  • Pedigree

MeSH Major

  • Calmodulin-Binding Proteins
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • DNA
  • Genetic Predisposition to Disease
  • Photoreceptor Cells, Vertebrate
  • Retinal Degeneration

abstract

  • To identify the causative mutations in two early-onset canine retinal degenerations, crd1 and crd2, segregating in the American Staffordshire terrier and the Pit Bull Terrier breeds, respectively. Retinal morphology of crd1- and crd2-affected dogs was evaluated by light microscopy. DNA was extracted from affected and related unaffected controls. Association analysis was undertaken using the Illumina Canine SNP array and PLINK (crd1 study), or the Affymetrix Version 2 Canine array, the "MAGIC" genotype algorithm, and Fisher's Exact test for association (crd2 study). Positional candidate genes were evaluated for each disease. Structural photoreceptor abnormalities were observed in crd1-affected dogs as young as 11-weeks old. Rod and cone inner segment (IS) and outer segments (OS) were abnormal in size, shape, and number. In crd2-affected dogs, rod and cone IS and OS were abnormal as early as 3 weeks of age, progressing with age to severe loss of the OS, and thinning of the outer nuclear layer (ONL) by 12 weeks of age. Genome-wide association study (GWAS) identified association at the telomeric end of CFA3 in crd1-affected dogs and on CFA33 in crd2-affected dogs. Candidate gene evaluation identified a three bases deletion in exon 21 of PDE6B in crd1-affected dogs, and a cytosine insertion in exon 10 of IQCB1 in crd2-affected dogs. Identification of the mutations responsible for these two early-onset retinal degenerations provides new large animal models for comparative disease studies and evaluation of potential therapeutic approaches for the homologous human diseases.

publication date

  • October 25, 2013

has subject area

  • Animals
  • Calmodulin-Binding Proteins
  • Cyclic Nucleotide Phosphodiesterases, Type 6
  • DNA
  • DNA Mutational Analysis
  • Disease Models, Animal
  • Dogs
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Male
  • Mutation
  • Pedigree
  • Photoreceptor Cells, Vertebrate
  • Retinal Degeneration

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3809947

Digital Object Identifier (DOI)

  • 10.1167/iovs.13-12915

PubMed ID

  • 24045995

Additional Document Info

start page

  • 7005

end page

  • 7019

volume

  • 54

number

  • 10