Goldstein Orly, Jordan Julie Ann, Aguirre Gustavo D, Acland Gregory M
Baker Institute for Animal Health, Cornell University College of Veterinary Medicine, Ithaca, NY.
Mol Vis. 2013 Aug 27;19:1871-84. eCollection 2013.
To identify the causative mutation of canine progressive retinal atrophy (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji breed of dog.
Basenji dogs were ascertained for the PRA phenotype by clinical ophthalmoscopic examination. Blood samples from six affected cases and three nonaffected controls were collected, and DNA extraction was used for a genome-wide association study using the canine HD Illumina single nucleotide polymorphism (SNP) array and PLINK. Positional candidate genes identified within the peak association signal region were evaluated.
The highest -Log10(P) value of 4.65 was obtained for 12 single nucleotide polymorphisms on three chromosomes. Homozygosity and linkage disequilibrium analyses favored one chromosome, CFA25, and screening of the S-antigen (SAG) gene identified a non-stop mutation (c.1216T>C), which would result in the addition of 25 amino acids (p.405Rext25).
Identification of this non-stop SAG mutation in dogs affected with retinal degeneration establishes this canine disease as orthologous to Oguchi disease and SAG-associated retinitis pigmentosa in humans, and offers opportunities for genetic therapeutic intervention.
确定在巴仙吉犬种中作为成年发病常染色体隐性疾病分离的犬进行性视网膜萎缩（PRA）的致病突变。
通过临床检眼镜检查确定巴仙吉犬的PRA表型。收集来自6例患病病例和3例未患病对照的血样，并使用犬HD Illumina单核苷酸多态性（SNP）阵列和PLINK进行全基因组关联研究的DNA提取。评估在峰值关联信号区域内鉴定出的位置候选基因。
在三条染色体上的12个单核苷酸多态性获得了最高的-Log10（P）值4.65。纯合性和连锁不平衡分析支持一条染色体CFA25，并且对S抗原（SAG）基因的筛选鉴定出一个不间断突变（c.1216T>C），这将导致添加25个氨基酸（p.405Rext25）。
在患有视网膜变性的犬中鉴定出这种不间断的SAG突变，将这种犬类疾病确定为与人类的小口病和SAG相关的色素性视网膜炎直系同源，并为基因治疗干预提供了机会。
