June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
A transcriptomic Approach to Refine the Primary Locus of a Canine Oligogenic Cone-Rod Dystrophy
Author Affiliations & Notes
  • Gautami Das
    School of Vet Medicine, Univ of Pennsylvania, Philadelphia, PA
  • Anand Swaroop
    National Eye Institute, NIH, Bethesda, MD
  • Matthew Brooks
    National Eye Institute, NIH, Bethesda, MD
  • Gustavo Aguirre
    School of Vet Medicine, Univ of Pennsylvania, Philadelphia, PA
  • Keiko Miyadera
    School of Vet Medicine, Univ of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships Gautami Das, None; Anand Swaroop, None; Matthew Brooks, None; Gustavo Aguirre, None; Keiko Miyadera, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 278. doi:
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      Gautami Das, Anand Swaroop, Matthew Brooks, Gustavo Aguirre, Keiko Miyadera; A transcriptomic Approach to Refine the Primary Locus of a Canine Oligogenic Cone-Rod Dystrophy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):278.

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

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Purpose: Cone-rod dystrophies (CRDs) cause cone dysfunction/loss prior to rod death, and eventually lead to blindness. A research colony was used to map a canine CRD (cord1) to a 14Mb interval on CFA15, and a homozygous exonic 44 bp insertion (ins/ins) resulting in a premature stop was identified in a positional candidate gene RPGRIP1. The interval was subsequently narrowed down to 1.74Mb still containing RPGRIP1. We have since identified a modifier locus, establishing an oligogenic model where a modifier controls the age of clinical onset of a cone-led retinal degeneration caused by homozygosity at the primary locus linked to RPGRIP1. In a recently reestablished research colony, however, some RPGRIP1ins/ins dogs still retain cone-ERG, while others develop no or severely diminished responses. Our aim was to refine the primary cord1 locus underlying cone-ERG loss.

Methods: months) or normal (n=2, 9-11 months). RNA-seq was performed by high-throughput sequencing of retinal cDNA libraries from these dogs using Illumina GAIIx, followed by assembly and analysis of the sequence reads. Differential expression of annotated and unannotated transcripts/genes was analyzed across the interval. Alternatively spliced isoforms of RPGRIP1 and other genes in the interval were assessed qualitatively and quantitatively. Based on sequence variants identified within the interval, haplotypes were constructed.

Results: Of the 24 annotated genes across the 1.74Mb cord1 primary locus critical interval, 23 showed retinal expression. Neither these genes nor their isoforms showed significant expressional difference between the two phenotypic groups. Additional reads were mapped within introns and immediate flanking regions of annotated genes. No new retinally expressed genes were identified within the interval. SNP-based haplotype analysis across this interval did not reveal any difference between the two studied groups.

Conclusions: Expression of known retinally expressed genes/transcripts across the cord1 primary locus was comparable in normal and cone loss RPGRIP1ins/ins dogs. The shared haplotype spanning the primary locus among all RPGRIP1ins/ins dogs regardless of the phenotype indicated the involvement of factor(s) beyond the critical interval in cone function loss.

Keywords: 539 genetics • 648 photoreceptors • 696 retinal degenerations: hereditary  

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