Progressive retinal atrophy (PRA), common autosomal recessive disorder affecting several dog breeds including Shih Tzu, is characterized by degeneration of photoreceptors leading to blindness. To identify PRA genetic variants, three affected and 15 unaffected Shih Tzu and 20 non-Shih Tzu were recruited. Dogs underwent ophthalmologic examination and electroretinography, revealing hallmark retina pathological changes and an abnormal electroretinography in all affected dogs but not in unaffected dogs. WGS was performed. Non-synonymous homozygous variants were searched in coding regions of genes involved in retinal diseases/development; the criterion was that variants should only be present in affected dogs and should be absent in both unaffected and 46 genomes of dogs (from an available evolutionary database). Only one out of the 109 identified variants is predicted to harbor a high-impact consequence, a nonsense c.452A>C (p.L151X) in the JPH2 gene. The genotype of JPH2 variant in all 38 dogs was determined with Sanger sequencing. All three affected dogs, but none of the 35 unaffected, were homozygous for the nonsense variant. JPH2 has been previously found to be expressed in several excitable cells/tissues including retina photoreceptors. Hence, JPH2 is a candidate gene for PRA in Shih Tzu.

中文翻译：

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全基因组测序鉴定出患有进行性视网膜萎缩的西施犬 JPH2 基因的纯合无义突变

进行性视网膜萎缩 (PRA) 是一种常见的常染色体隐性遗传疾病，影响包括西施犬在内的几种犬种，其特征是光感受器退化导致失明。为了识别 PRA 遗传变异，招募了 3 名受影响的西施犬和 15 名未受影响的西施犬和 20 名非西施犬。狗接受了眼科检查和视网膜电图检查，发现所有受影响的狗都有标志性的视网膜病理变化和异常的视网膜电图，但未受影响的狗没有。进行了WGS。在涉及视网膜疾病/发育的基因的编码区中搜索了非同义纯合变体；标准是变异应该只存在于受影响的狗中，并且在未受影响的狗和 46 个基因组中都应该不存在（来自可用的进化数据库）。JPH2基因。所有38只犬的JPH2变异基因型均通过Sanger测序确定。所有三只受影响的狗，但 35 只未受影响的狗都不是无意义变体的纯合子。先前已发现JPH2在包括视网膜光感受器在内的几种可兴奋细胞/组织中表达。因此，JPH2是西施犬 PRA 的候选基因。