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

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

Single-gene trait/disorder: yes

Mode of inheritance: X-linked

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2010

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.

Species-specific symbol: HA

History: None of the haemophiliac sheep described by Neuenschwander and Pliska (1990) and studied by Neuenschwander et al. (1992), Neuenschwander and Pliska (1994) and Backfisch et al. (1994) survived, and hence this line of sheep had become extinct. However, a few straws of semen had been retained, and from these, Porada et al. (2010) were able to recreate the haemophiliac line of sheep, which should be a valuable animal model.

Mapping: Using in situ hybridization with a 3-kb fragment of human F8C cDNA, Backfisch et al. (1994) mapped the ovine F8C gene to Xq24-q33.

Markers: In Swiss sheep, an RFLP detected with a 1.8-kb SstI/KpnI fragment of the cDNA of the human F8C gene, detects a 5.8 kb band which is associated with the mutant allele (Backfisch et al., 1994).

Molecular basis: By sequencing the obvious candidate gene (F8), Porada et al. (2010) "identified an 11 bp region in exon 14 that differed between the wild-type and the hemophiliac. Importantly, this difference introduced a premature stop codon at base position 3112–4 in exon 14, as is seen in some human HA patients. This mutation also included a single nucleotide insertion-induced frame shift, creating five additional stop codons within the next 183 bp, precluding protein translation past this point, and providing a molecular explanation for the severe phenotype".

Breed: Weißes Alpenschaf, Switzerland (Sheep) (VBO_0015510).
Breeds in which the phene or likely causal variants have been documented. If a likely causal variant has been documented, see variant-specific breed information in the variant table. (Breed information may be incomplete).

Associated gene: