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T. N. Kuznetsova, A. Komaromy, S. Pearce-Kelling, G. M. Acland, G. Aguirre; Identification of Novel Canine RPGRIP1 Splice Variants and New Mutation Affecting Splicing of 3’-Terminal Alternative Exon. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3099.
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Standard techniques were used to characterize cRPGRIP1 isoforms and its polymorphism. Blood samples of miniature longhaired dachshunds (MLHD) and English Springer Spaniels (ESS) were received from the OptiGen®, LLC.
Analysis of the C-terminal cRPGRIP1 sequence indicated the existence of a group of cRPGRIP1 transcripts that were alternative processed, and involved inclusion of a 3’-terminal exon 20C that eliminated the RPGR-interacting domain. The middle segment of those transcripts also is quite truncated in comparison to full-length variant. One transcript arises from skipping exons 14-19. The second lacks exons 14-18, and the third is generated by skipping exons 14-16. A 3 nucleotide deletion (Δ3) comprising the splice acceptor site and first nucleotide of exon 20C was identified in MLHD dog which had been diagnosed with crd. The same dog had also a 44 nt insertion (Ins44) in exon 2 (Mellersh et al., 2006), and showed an ERG with profound changes. We investigated distribution of the new mutation in several pedigrees of MLHD and ESS dogs which had been already genotyped with the exon 2 insertion. It was found that in most, but not all cases, the Δ3 genotype coincided with Ins44. However, haplotype analysis did not show strong association of double homozygous genotype with crd.
Three novel alternatively spliced isoforms of cRPGRIP1 and the new mutation eliminating splicing site were identified. We conclude that homozygous genotype of Δ3 may increase the risk of crd, but the mutation by itself is not sufficient to cause disease.
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