A non-allelic homologous recombination-induced inversion in intron 22 of the F8 gene is causative for haemophilia A in a Weimaraner male dog
- 1Institute of Veterinary Medicine, Georg-August-University of Göttingen, Göttingen, Germany.
- 2Universidade Federal do Vale do São-Francisco, Petrolina, Brazil.
Abstract
Haemophilia A is a severe coagulation disorder caused by partial or complete loss of function of the X-chromosomal F8 gene. It is a relatively common coagulation disorder that has been reported in at least 17 dog breeds to date. However, only five distinct molecular causes have been identified so far. One molecular genetic cause is a large inversion, which has also been described in humans and was first studied in a research colony of Irish Setters at the University of North Carolina at Chapel Hill. However, the exact location of the inversion breakpoint junctions in dogs has not been determined. Here, we describe the molecular analysis of a case of haemophilia A in a Weimaraner dog family using long-read sequencing. We show that the cause of haemophilia A is an approximately 420kb inversion affecting the F8 gene. The breakpoints of the inversion were identified in intron 22 at position 124,003,000 and between chloride intracellular channel 2 (CLIC2) and epsilon-trimethyllysine hydroxylase (TMLHE) at position 124,432,668 (NC_049260.1:g.124003000_124432668inv). As in humans, the inversion is most likely caused by non-allelic homologous recombination between intron 22 and a region approximately 420kb downstream of the F8 gene. By identifying the inversion breakpoint junctions, it is now possible to test carriers of the disorder at the DNA level and thus prevent the risk of disease in male offspring.
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BibTeX
@article{pach2026nonallelic,
title = {{A non-allelic homologous recombination-induced inversion in intron 22 of the F8 gene is causative for haemophilia A in a Weimaraner male dog}},
author = {Sabrina Pach and Joel Fonseca Nogueira and Bertram Brenig},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0360975},
url = {https://doi.org/10.1371/journal.pone.0360975},
note = {CC BY},
}
RIS
TY - JOUR
TI - A non-allelic homologous recombination-induced inversion in intron 22 of the F8 gene is causative for haemophilia A in a Weimaraner male dog
AU - Sabrina Pach
AU - Joel Fonseca Nogueira
AU - Bertram Brenig
PY - 2026
DA - 2026/10/26
JO - PLOS One
DO - 10.1371/journal.pone.0360975
UR - https://doi.org/10.1371/journal.pone.0360975
AB - Haemophilia A is a severe coagulation disorder caused by partial or complete loss of function of the X-chromosomal F8 gene. It is a relatively common coagulation disorder that has been reported in at least 17 dog breeds to date. However, only five distinct molecular causes have been identified so far. One molecular genetic cause is a large inversion, which has also been described in humans and was first studied in a research colony of Irish Setters at the University of North Carolina at Chapel Hill. However, the exact location of the inversion breakpoint junctions in dogs has not been determined. Here, we describe the molecular analysis of a case of haemophilia A in a Weimaraner dog family using long-read sequencing. We show that the cause of haemophilia A is an approximately 420kb inversion affecting the F8 gene. The breakpoints of the inversion were identified in intron 22 at position 124,003,000 and between chloride intracellular channel 2 (CLIC2) and epsilon-trimethyllysine hydroxylase (TMLHE) at position 124,432,668 (NC_049260.1:g.124003000_124432668inv). As in humans, the inversion is most likely caused by non-allelic homologous recombination between intron 22 and a region approximately 420kb downstream of the F8 gene. By identifying the inversion breakpoint junctions, it is now possible to test carriers of the disorder at the DNA level and thus prevent the risk of disease in male offspring.
SN - 1932-6203
ER -