OMIA 000437-9913 : Haemophilia A in Bos taurus

In other species: dog , domestic cat , horse , pig , sheep

Possibly relevant human trait(s) and/or gene(s) (MIM number): 306700

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: German Fleckvieh, Japanese Brown.

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
German Fleckvieh Haemophilia A F8 missense UMD3.1 X g.38842314A>T p.His45Leu ss213751737 2018 29774585
Japanese Brown Haemophilia A F8 missense UMD3.1 X g.38971744T>A c.6458T>A p.L2153H 2009 19456318 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

References


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., WeiƟ, 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.

Edit History


  • Created by Frank Nicholas on 10 Jul 2009
  • Changed by Frank Nicholas on 07 Oct 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 02 Mar 2019