Coagulation Factor VIII

The Coagulation Factor VIII Gene, known as F8, is located on the X chromosome. Most cases of Hemophilia are caused by a mutation on the F8 gene that produces the Factor VIII. The mutation is often caused by point mutations or inversions that lead to a disruption of the factor creation. Lakich et al (1993) found in approximately 45% of families with severe disease “recombination between the homologous F8A sequences within intron 22 and upstream of the F8 gene. Such a recombination would lead to an inversion of all intervening DNA and a disruption of the gene.” Furthermore, in a study of 147 cases of severe hemophilia A, done by Becker et al. (1996) found a “causative defect in the F8 gene in 126 patients (85.7%). An inversion of the gene was found in 55 patients (37.4%), a point mutation in 47 (32%), a small deletion in 14 (9.5%), a large deletion in 8 (5.4%), and a small insertion in 2 (1.4%). “

More Gene information can be found here: RefSeq Gene Information, and

FASTA Gene Sequence.

Coagulation factor protein VIII is produced from this gene:

The Coagulation factor VIII protein is very important in the blood coagulation cascade that results in blood clots forming.  

A video explaining the coagulation cascade:  

An even simpler explanation:

Those with the Hemophilia disorder A have a mutation that leads to the production of faulty Coagulation factor VIII protein; this mutation is often caused by a point mutations: inversions, deletions, or missense mutations

To give a very simple example of what a point mutation is, using words in place of codons, instead of the DNA's message being, "the cat sleeps", it could be either, "the cat 'sleeps'" (silent mutation),  "the cat ... " (nonsense), or "the cat runs" (missense). 

Additionally, the Coagulation factor VIII protein is highly conserved amongst organisms. The Coagulation factor VIII protein is a very efficient way to coagulate blood and thus has been maintained from a common ancestor through several species. Making a phylogeny tree of the Coagulation factor VIII you would see that humans and chimpanzees both have a highly related Coagulation factor VIII - but you would also see that humans and Danio Rerio (zebrafish) are also very closely related. For this reason animals research is very important to helping learn more about and treat Hemophilia.  

 

References: 

Becker, J., Schwaab, R., Moller-Taube, A., Schwaab, U., Schmidt, W., Brackmann, H. H., Grimm, T., Olek, K., Oldenburg, J. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies. Am. J. Hum. Genet. 58: 657-670 (1996)

Bowen, D. J. "Haemophilia A and haemophilia B: molecular insights." Molecular Pathology 55.1 (2002): 1

ChristensenUniversity of Wisconsin-Madison, Allison. "Phylogeny."Coagulation Factor VIII and Hemophilia A. University of Wisconsin-Madison, 19 May 2013. Web. 19 July 2014.

"Coagulation Cascade." YouTube. Ferrosan Medical Devices10, 10 Sept. 2010. Web. 07 Aug. 2014.

Naoum, Paulo C., and Alia F. Naoum. "Hemostasis, Coagulation and Fibrinolisis." YouTube. YouTube, 12 Mar. 2010. Web. 07 Aug. 2014

Lakich, D., Kazazian, H. H., Jr., Antonarakis, S. E., Gitschier, J. Inversions disrupting the factor VIII gene are a common cause of severe haemophilia A. Nature Genet. 5: 236-241, (1993)

"Point Mutation." Wikipedia. Wikimedia Foundation, 08 Feb. 2014. Web. 02 Aug. 2014.

"The Genomic Era !" The Genomic Era ! N.p., n.d. Web. 02 Aug. 2014.