A SINE Insertion in F8 Gene Leads to Severe Form of Hemophilia A in a Family of Rhodesian Ridgebacks

• Published in: Genes Vol. 12; no. 2; p. 134
• Main Authors: Kehl, Alexandra, Haaland, Anita Haug, Langbein-Detsch, Ines, Mueller, Elisabeth
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-01-2021; MDPI
• Subjects: Age; Animal euthanasia; Breeding; Breeding of animals; Coagulation factors; Consortia; Deoxyribonucleic acid; Disease; DNA; Dogs; Factor VIII deficiency; Families & family life; Genetic diversity; Genomes; Hemophilia; Hospitals; Insertion; Life sciences; Males; Mutation; Polymorphism; Short interspersed nucleotide elements; Siblings; Software; Veterinary services; X chromosomes; United States > US; mutation; dog; hemostasis disorder
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12020134

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
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
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.