Haemophilia Within The British Royal Family

Assuming I am a genetic counsellor, I will try to predict future outcomes and provide possible solutions of the genetic disorder known as haemophilia.

In this case study I will be looking at the pedigree chart of the British Royal family and their long past history with the genetic disorder, haemophilia type B. In order to do this I will produce various genetic crosses of the past generations of the royal family in order to observe how the defected gene causing haemophilia has been passed down and inherited over the generations and I will also be making future predictions in order to conclude how the occurrence of this disorder can be reduced or eliminated.

Haemophilia is a blood disorder whereby the blood does not clot properly. When skin tissues are ruptured, the blood that is being carried through the body s network of blood vessels is able to leak out of these ruptured vessels causing blood loss. The normal mechanisms of the human body enable clots of blood to form ensuring the vessel can be sealed over, ultimately halting blood loss.

Genetics behind the disease

Coagulation factors work alongside each other in the blood clotting mechanism to prevent and stop blood loss due to injury (Furie, 2014). The F8 gene is responsible for delivering the instructions for making the protein needed for the clotting mechanism, this protein in called coagulation factor VIII. Mutations in this F8 gene cause haemophilia A. The F9 gene is responsible for delivering the instructions for making the protein needed for the clotting mechanism, this protein in called coagulation factor IX. Mutations in this F9 gene cause haemophilia B. Any type of mutations in these genes responsible for making these factors can lead to abnormal coagulations factors being produced or decreased amounts of these factors being produced

Discussion

In relation to the British Royal family we can see that haemophilia was first recognised in Queen Victoria of England (a carrier). Queen Victoria passed the mutated F9 gene, responsible for delivering the instructions for making the protein called coagulation factor IX to three of her nine children, two of which where female carriers (Alice and Beatrice) and one male sufferer (Leopold). Alice s daughter (Alix) was a carrier and married the Emperor of Russia (Nicholas II) (Buxhoeveden 1930). The disorder was passed down through Queen Victoria s descendants affecting three European Royal families by marriage into the Russian, Spanish and also German Royals (Rohl, J. et al., 1999).

We can also see from this pedigree chart that haemophilia may shorten the life expectancy as many sufferers of the disorder died or did not further procreate to pass the disorder to their possible offspring. This in turn shortened the family line of many of the individuals whom suffered with haemophilia B within the Royal family. The reason in which the Royal families marry into other Royal families (Royal intermarriage) was to keep the Royal blood within the family thus forming a political alliance also know as an elite class. Although this is a good way to limit outsiders entering into the Royal family, it also increases the chances of inherited disorders to be more prevalent as marrying within a family can heighten the amount of individuals whom are susceptible to any inherited disorder due to a limited gene pool. Negative traits such as inherited diseases are only able to become widespread when a population is left to reproduce within its own people. Recent times have proved different to the past traditions of marrying within the family with the addition of new blood into the family. Introducing new blood increases the gene pool (genetic diversity) ultimately allowing increased chance of long-term survival.

Treatments and cure

There are two types of treatments available for haemophilia sufferers, preventative and on demand treatment. Preventative treatments include prophylaxis for severe cases and demands regular injections of clotting factors. On demand treatments are used mainly for moderate suffers of haemophilia and requires on demand administration of treatment, this involves an injection of clotting factors.

Gene therapy is the most credible cure being researched and applied at present. Gene therapy works by isolating cells from the affected individual (typically liver cells) and genetically reprogramming these cells to encode the instructions for making the proteins needed for blood coagulation. These altered cells and now reintroduced into the body where they can actively take part in the blood clotting mechanism. Between the years of 1998 and 2001 different clinical trials took place in order to treat haemophilia by means of gene transfer. Some of which include, Adeno associated virus or AAV vectors in the transfer and expression of the coagulation factor IX for treatment of haemophilia type B sufferers (Kay et al, 2000) and non-viral vectors in the transfer and expression of coagulation factor VIII for treatment of haemophilia type A sufferers (Roth et al, 2001). Recent advancements in treatments for haemophilia include the use of retroviral vectors with developments in lentiviral vectors (Murphy and High, 2008). Lentiviral vectors are a type of retrovirus that are able to infect both dividing and also non-dividing cells due to their pre-integration complex that can penetrate the intact membrane of the nucleus of a target cell (Kendall, 2014). As mentioned above gene therapy is a credible cure against haemophilia and with new advancements in the study of gene therapy such as liposome use there is a firm foundation to a possible cure for haemophilia type A (Yin J, 2015). The use of liposomes as a vector in gene therapy is an exciting new approach to curing genetic mutations and has far less associated complications involved in comparison to previous techniques.

Recommendations

Recommendations in order to reduce the occurrence of the haemophilia and prevent it being passed down in the Royal family could include genetic counselling. Genetic counselling is offered to sufferers, carriers and also the family of these haemophilic individuals to provide advice on their future choices on having children and whether their children are likely to be effected by the disorder. For example a suffer of haemophilia would be highly advised not to have children with another suffer as this will result in all of their children inheriting the disorder and being affected by haemophilia. Genetic counselling allows sufferers and carriers of haemophilia to make more informed decisions about their future and also impacts on the reduction on the disorder altogether in their family line if advice is acted upon. Important steps that can be taken to diagnose haemophilia during pregnancy can include tests such as chorionic villus sampling or amniocentesis. Both tests can help to indicate if the child has the mutated gene causing haemophilia.

Conclusion

After conducting this case study it has become apparent that society as a whole has the greatest influence in preventing and restricting future generations from being affected from genetic diseases and disorders. It is important that society takes action in terms of safeguarding their family line by carrying out regular health checks and guidance in future family planning. Although there are various treatments such as preventative and on demand and also possible cures using lentiviral vectors for haemophilia, prevention in its own right is the greatest measure to safeguard the future generations from any genetic disorder.