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Doreen Becker, Ausra Milano, Sue Pearce-Kelling, Gustavo D Aguirre; A genetic and candidate gene association study for optic nerve hypoplasia in dogs. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2537.
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Optic nerve hypoplasia (ONH) is a rare genetic defect leading to blindness, likely due to failure of retinal ganglion cell development; one or both eyes may be affected. About 0.8% of poodles, particularly miniature varieties are affected with ONH. Fundus phenotypes are highly variable, which makes clinical characterization difficult. The prognosis is poor in most cases and there is no treatment available. We conducted a candidate gene association study with five genes that are associated with ocular malformations and are typically expressed in ganglion cells.
Samples from phenotype ascertained animals and samples of their non-affected relatives together with their eye exam and pedigree information were obtained from veterinary ophthalmologists in the US and different centers in Europe. We obtained archival tissue samples of cases confirmed by clinical and pathological examinations. DNA was extracted and used for PCR amplification. Candidate genes were selected based on the reported findings about the association with the same or similar disease in other species, as well as the knowledge about the gene’s biological function (OTX2, SOX2, PAX6, TUBA1A and TUBA8). The coding exons and the intron-exon boundaries of these genes were sequenced in three cases and three controls and were screened for associated variants to the disease. Additionally, we sequenced known SNPs from dbSNP in the 5’- and the 3’-UTR.
We were able to assemble a pedigree connecting all affected animals to a possible common founder. We identified 12 variants in the introns of OTX2, SOX2, PAX6 and TUBA1A and a synonymous variant in the coding sequence of SOX2. All variants did not segregate with the phenotype.
The inheritance pattern for ONH is still unclear, but the pedigree suggests an autosomal recessive transmission. There is no association between identified variants as well as between SNP haplotypes and ONH. Therefore, OTX2, SOX2, PAX6, TUBA1A and TUBA8 can be ruled out as causative genes for ONH in dogs.
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