OMIA 000437-9940 : Haemophilia A in Ovis aries |
In other species:
domestic cat
,
dog
,
horse
,
pig
,
cattle
,
crab-eating macaque
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers):
306700 (trait)
,
300841 (gene)
Mendelian trait/disorder:
yes
Mode of inheritance:
X-linked
Considered a defect:
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:
Swiss Alpine.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| F8 | coagulation factor VIII, procoagulant component | Ovis aries | X | NC_056080.1 (81474456..81336898) | 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.
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 621 | Swiss Alpine | Haemophilia A | F8 | delins, small (<=20) | Naturally occurring variant | Oar_rambouillet_v1.0 | X | g.86301507_86301516delinsTAATTAATACC | c.3108_3117delinsGGTATTAATTA | The 11 bp region in exon 14 that differed between the wild-type and the hemophiliac introduced a premature stop codon | 2010 | 19943872 | The genomic location on Oar_rambouillet_v1.0 was determined by Katie Eager, EMAI, NSW Department of Primary Industries. 210906 After checking the cDNA sequence in Fig. 3 of the paper, FN concluded that the 10bp deletion starts at c.3108 and ends at c.3117 and that the 11bp inserted sequence is GGTATTAATTA. Thus the HGVS-consistent notation is c.3108_3117delinsGGTATTAATTA, instead of c.3107del10ins11. |
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.
| 2021 | Arruda, V.R., Weber, J., Samelson-Jones, B.J. : | |
| Gene therapy for inherited bleeding disorders. Semin Thromb Hemost 47:161-173, 2021. Pubmed reference: 33636747. DOI: 10.1055/s-0041-1722862. | ||
| 2016 | Yen, C.T., Fan, M.N., Yang, Y.L., Chou, S.C., Yu, I.S., Lin, S.W. : | |
| Current animal models of hemophilia: the state of the art. Thromb J 14:22, 2016. Pubmed reference: 27766048. DOI: 10.1186/s12959-016-0106-0. | ||
| 2012 | Porada, C.D., Almeida-Porada, G. : | |
| Treatment of Hemophilia A in Utero and Postnatally using Sheep as a Model for Cell and Gene Delivery. J Genet Syndr Gene Ther S1:, 2012. Pubmed reference: 23264887. DOI: 10.4172/2157-7412.S1-011. | ||
| Zakas, P.M., Gangadharan, B., Almeida-Porada, G., Porada, C.D., Spencer, H.T., Doering, C.B. : | ||
| Development and Characterization of Recombinant Ovine Coagulation Factor VIII. PLoS One 7:e49481, 2012. Pubmed reference: 23152911. DOI: 10.1371/journal.pone.0049481. | ||
| 2011 | Porada, C.D., Sanada, C., Kuo, C.J., Colletti, E., Mandeville, W., Hasenau, J., Zanjani, E.D., Moot, R., Doering, C., Spencer, H.T., Almeida-Porada, G. : | |
| Phenotypic correction of hemophilia A in sheep by postnatal intraperitoneal transplantation of FVIII-expressing MSC. Exp Hematol 39:1124-1135.e4, 2011. Pubmed reference: 21906573. DOI: 10.1016/j.exphem.2011.09.001. | ||
| 2010 | Porada, C.D., Sanada, C., Long, C.R., Wood, J.A., Desai, J., Frederick, N., Millsap, L., Bormann, C., Menges, S.L., Hanna, C., Flores-Foxworth, G., Shin, T., Westhusin, M.E., Liu, W., Glimp, H., Zanjani, E.D., Lozier, J.N., Pliska, V., Stranzinger, G., Joerg, H., Kraemer, D.C., Almeida-Porada, G. : | |
| Clinical and molecular characterization of a re-established line of sheep exhibiting hemophilia A. J Thromb Haemost 8:276-85, 2010. Pubmed reference: 19943872. DOI: 10.1111/j.1538-7836.2009.03697.x. | ||
| 1994 | Backfisch, W., Neuenschwander, S., Giger, U., Stranzinger, G., Pliska, V. : | |
| Carrier detection of ovine hemophilia A using an RFLP marker, and mapping of the factor VIII gene on the ovine X-chromosome Journal of Heredity 85:474-478, 1994. Pubmed reference: 7995928. | ||
| Neuenschwander, S., Pliska, V. : | ||
| Factor VIII in blood plasma of haemophilic sheep: Analysis of clotting time-plasma dilution curves Haemostasis 24:27-35, 1994. Pubmed reference: 7959353. | ||
| 1992 | Neuenschwander, S., Kisslingalbrecht, L., Heiniger, J., Backfisch, W., Stranzinger, G., Pliska, V. : | |
| Inherited Defect of Blood Clotting Factor-VIII (Haemophilia- A) in Sheep Thrombosis and Haemostasis 68:618-620, 1992. Pubmed reference: 1455410. | ||
| 1990 | Neuenschwander, S., Pliska, V. : | |
| Hemophilia in Sheep and the Use of Sheep in Blood Coagulation Research Journal of Animal Breeding and Genetics-Zeitschrift Fur Tierzuchtung und Zuchtungsbiologie S5:155-164, 1990. |
Edit History
- Created by Frank Nicholas on 16 Jul 2005
- Changed by Frank Nicholas on 03 Dec 2012
- Changed by Frank Nicholas on 22 May 2020