ArticleProceedings of the National Academy of Sciences of the United States of America2002
The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 102 citations in OpenAlex.
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- Hemophilia A: An Ideal Disease for Prenatal Therapy.Prenatal diagnosis · 2025Review
- Article
- Ultrasound-mediated gene delivery of factor VIII plasmids for hemophilia A gene therapy in mice.Molecular therapy. Nucleic acids · 2022Article
- Article
- A SINE Insertion inGenes · 2021Article
- A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells.Nature biotechnology · 2021Article
- Recurrent inversion toggling and great ape genome evolution.Nature genetics · 2020Article
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
- Translational Potential of Immune Tolerance Induction by AAV Liver-Directed Factor VIII Gene Therapy for Hemophilia A.Frontiers in immunology · 2020Review
- Infused factor VIII-expressing platelets or megakaryocytes as a novel therapeutic strategy for hemophilia A.Blood advances · 2019Article
- Gene therapy for hemophilia: what does the future hold?Therapeutic advances in hematology · 2018Review
- Canine and Feline Models of Human Genetic Diseases and Their Contributions to Advancing Clinical Therapies .The Yale journal of biology and medicine · 2017Review
- Article
- Factor VIII associated with lipidic nanoparticles retains efficacy in the presence of anti-factor VIII antibodies in hemophilia A mice.Biopharmaceutics & drug disposition · 2016Article
- Soy Phosphatidylinositol-Containing Lipid Nanoparticle Prolongs the Plasma Survival and Hemostatic Efficacy of B-domain-Deleted Recombinant Canine Factor VIII in Hemophilia A Dogs.Journal of pharmaceutical sciences · 2016Article
- Characterization of a genetically engineered mouse model of hemophilia A with complete deletion of the F8 gene.Journal of thrombosis and haemostasis : JTH · 2016Article
- Current animal models of hemophilia: the state of the art.Thrombosis journal · 2016Review
- Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII.Comparative medicine · 2016Article
- In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application.Molecular therapy. Methods & clinical development · 2016Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
In the Chapel Hill colony of factor VIII-deficient dogs, abnormal sequence (ch8, for canine hemophilia 8, GenBank no. ) follows exons 1-22 in the factor VIII transcript in place of exons 23-26. The canine hemophilia 8 locus (ch8) sequence was found in a 140-kb normal dog genomic DNA bacterial artificial chromosome (BAC) clone that was completely outside the factor VIII gene, but not in BAC clones containing the factor VIII gene. The BAC clone that contained ch8 also contained a homologue of F8A (factor 8 associated) sequence, which participates in a common inversion that causes severe hemophilia A in humans. Fluorescence in situ hybridization analysis indicated that exons 1-26 normally proceed sequentially from telomere to centromere at Xq28, and ch8 is telomeric to the factor VIII gene. The appearance of an "upstream" genomic sequence element (ch8) at the end of the aberrant factor VIII transcript suggested that an inversion of genomic DNA replaced factor VIII exons 22-26 with ch8. The F8A sequence appeared also in overlapping normal BAC clones containing factor VIII sequence. We hypothesized that homologous recombination between copies of canine F8A inside and outside the factor VIII gene had occurred, as in human hemophilia A. High-resolution fluorescent in situ hybridization on hemophilia A dog DNA revealed a pattern consistent with this inversion mechanism. We also identified a HindIII restriction fragment length polymorphism of F8A fragments that distinguished hemophilia A, carrier, and normal dogs' DNA. The Chapel Hill hemophilia A dog colony therefore replicates the factor VIII gene inversion commonly seen in humans with severe hemophilia A.
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