In other species: crab-eating macaque , dog , domestic cat , horse , pig , sheep

Categories: Haematopoietic system phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 306700 (trait) , 300841 (gene)

Links to relevant human diseases in MONDO:

• MONDO:0010602: hemophilia A

Mendelian trait/disorder: yes

Mode of inheritance: X-linked recessive

Disease-related: 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).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: