Hemophilia A is the most common coagulation factor disorder in humans and dogs. The disease is characterized by the lack or diminished activity of Factor VIII (FVIII), caused by variants in the F8 gene and inherited as an X chromosomal trait. Two related male Rhodesian Ridgebacks were diagnosed with Hemophilia A due to reduced FVIII activity. The purpose of the study was to determine the genetic cause and give breeding advice for the remaining family members in order to eradicate the variant. By Sanger sequencing a short interspersed nuclear element (SINE) insertion in exon 14 of the F8 gene was found. Perfect correlation of this genetic variant with clinical signs of hemophilia A in the family tree, and the lack of this genetic variant in more than 500 unrelated dogs of the same and other breeds, confirms the hypothesis of this SINE being the underlying genetic cause of Hemophilia A in this family. The identification of clinically unaffected female carriers allows subsequent exclusion of these animals from breeding, to avoid future production of clinically affected male offspring and more subclinical female carriers.

中文翻译：

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F8 基因中的 S​​INE 插入导致罗得西亚脊背犬家族出现严重的 A 型血友病

血友病 A 是人类和狗中最常见的凝血因子疾病。该疾病的特征在于因子 VIII (FVIII) 的活性缺乏或减弱，该因子由 F8 基因中的变异引起并作为 X 染色体特征遗传。由于 FVIII 活性降低，两只相关的雄性罗得西亚脊背犬被诊断出患有 A 型血友病。该研究的目的是确定遗传原因并为其余的家庭成员提供育种建议，以根除该变异。通过 Sanger 测序发现 F8 基因的外显子 14 中插入了一个短的散在核元件 (SINE)。这种遗传变异与家谱中血友病 A 的临床症状完全相关，并且在 500 多只相同和其他品种的无关狗中缺乏这种遗传变异，证实了这种 SINE 是该家族中血友病 A 的潜在遗传原因的假设。鉴定临床未受影响的雌性携带者允许随后将这些动物排除在繁殖之外，以避免将来产生临床受影响的雄性后代和更多亚临床雌性携带者。