OMIA:000437-9913 : Haemophilia A in Bos taurus
In other species: domestic cat , dog , horse , pig , sheep , crab-eating macaque
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 306700 (trait) , 300841 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: X-linked recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2009
Cross-species summary: Also called factor VIII deficiency. Impaired coagulability of the blood, with a consequential strong tendency to bleed, due to a deficiency of clotting factor VIII. Since the gene for this factor is located on the X chromosome, the disorder is expected to be X-linked. As with haemophilia B, this expectation has been confirmed in all species of mammal in which the disorder has been reported. In humans, there are hundreds of different mutations that give rise to haemophilia A. In domesticated animals, the disorder has been reported in a large range of species.
Molecular basis: Khalaj et al. (2009): "A nucleotide substitution of T to A resulting in an amino acid substitution of leucine to histidine (p.Leu2153His) was identified in a highly conserved residue in the C1 domain of factor VIII. Genotyping of 254 normal animals including the pedigree of the affected animals and randomly sampled animals of different breeds confirmed that the substitution is the causative mutation of cattle haemophilia A."
Analysis of whole-genome sequence from a German Fleckvieh bull affected with a mild form of this disorder and from 19 non-affected cattle from other breeds enabled Reinartz et al. (2018) to identify a likely causal missense variant, namely ss213751737:g.38842314A>T; p.His45Leu in the F8 gene. A synonymous variant ss2137517373:g.38884774G>A; p.Ala361Ala was in complete disequilibrium with the former variant.
Prevalence: Reinartz et al. (2018): "The frequency of the mutant alleles T and A were 6/121 chromosomes in the herd of origin."
Breeds: Fleckvieh-Simmental, Germany (Cattle) (VBO_0002354), Japanese Brown, Japan (Cattle) (VBO_0004988).
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|F8||coagulation factor VIII||Bos taurus||X||NC_037357.1 (36013125..36155734)||F8||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|1038||Fleckvieh-Simmental, Germany (Cattle)||Haemophilia A||F8||missense||Naturally occurring variant||ARS-UCD1.2||X||g.36017426A>T||c.134A>T||p.(H45L)||ENSBTAT00000036726.5:c.134A>T; ENSBTAP00000036581.4:p.His45Leu||rs1117392179||rs1117392179||2018||29774585|
|194||Japanese Brown, Japan (Cattle)||Haemophilia A||F8||missense||Naturally occurring variant||ARS-UCD1.2||X||g.36145188T>A||c.6458T>A||p.(L2153H)||2009||19456318||Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool|
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2018||Reinartz, S., Weiß, C., Mischke, R., Distl, O. :|
|A mild form of haemophilia A is associated with two factor VIII missense mutations in German Fleckvieh cattle. Anim Genet 49:350-351, 2018. Pubmed reference: 29774585 . DOI: 10.1111/age.12672.|
|2009||Khalaj, M., Abbasi, AR., Shimojo, K., Moritomo, Y., Yoneda, K., Kunieda, T. :|
|A missense mutation (p.Leu2153His) of the factor VIII gene causes cattle haemophilia A. Anim Genet 40:763-765, 2009. Pubmed reference: 19456318 . DOI: 10.1111/j.1365-2052.2009.01906.x.|
|2008||Moritomo, Y., Shimojo, K., Miyadera, K., Khalaj, M., Asano, Y., Kunieda, T., Ogawa, H. :|
|Clinical and pathological aspects of hemophilia a in Japanese Brown cattle. J Vet Med Sci 70:293-6, 2008. Pubmed reference: 18388431 .|
|1984||Healy, P.J., Sewell, C.A., Exner, T., Morton, A.G., Adams, B.S. :|
|Haemophilia in Hereford cattle: factor VIII deficiency. Aust Vet J 61:132-3, 1984. Pubmed reference: 6743161 .|
|1982||Dodds, W.J. :|
|An effective mass-screening program for animal models of the inherited bleeding disorders. Prog Clin Biol Res 94:117-32, 1982. Pubmed reference: 6981819 .|
- Created by Frank Nicholas on 10 Jul 2009
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