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Royal Blood and DNA

This piece of SangerArt that I call “Royal Blood and DNA” combines science, art and history all in one image. Read on to find out more about the inspiration behind it.

You may recognise the figures in this family portrait as Queen Victoria, Prince Albert and their 9 children. It is well known that Queen Victoria passed on the blood clotting disorder haemophilia to her youngest son Prince Leopold and also through 2 of her daughters - Princess Alice and Princess Beatrice to many male descendants in the European Royal dynasties, including German and Spanish Princes and most famously the heir to the Russian throne Tsarevich Alexei who was murdered along with his family by Bolshevik revolutionaries in 1918.

Hence haemophilia is known as the Royal disease. It is an X-linked recessive disease and is usually passed from female carriers to, on average, 50% of their sons and consequently is much more commonly seen in males than females.

It can be caused by defects in the blood clotting factors VIII or IX, encoded by the F8 and F9 genes, both located on the X chromosome. As a result, the blood of males that are hemizygous and females that are homozygous for mutations in F8 or F9 does not clot properly. This can result in life threatening blood loss from only minor internal or external injuries and historically this resulted in early death for many affected boys and young men. Fortunately there are now treatments available, made possible by scientific research into the causes of the disease, that have improved the lives of haemophiliacs today.

This artwork was inspired by research led by Evgeny Rogaev, that sequenced DNA extracted from the remains of the Romanov family (including Tsarevich Alexei). From this research we now know that the Royal disease was caused by a mutation in the F9 gene and was therefore the rarer form of the disease - haemophilia B. This research was published in the journal Science in 2009.

F9-all layers-Victoria Royal Family v5_2
Royal Blood - annotations - key.jpg
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This is an example of a single nucleotide change that quite possibly changed the course of history. It is often said that the influence on the Russian Royal family of the mystic healer Rasputin, who helped the young Tsarevich with his haemophilia, contributed in part to the downfall of the Romanovs and the Bolshevik revolution of 1917.

The artwork is made up of >8000 bases of Sanger DNA sequence chromatogram with the image of Queen Victoria, Prince Albert and their nine children embedded into it. There are 27 rows of sequence at 300 bases across, designed to be printed at a minimum size of around 22 in or 55 cm across.

In this artwork, I have used sequence from the F9 gene combined with a portrait of Queen Victoria and her family made by John Jabez Edwin Mayall, circa 1861. The only person with haemophilia in this image is a young Prince Leopold in the centre, the first known sufferer of the Royal disease. I have positioned the single base change that caused his disease over his heart and used red shadowing over him and the other 3 female carriers of the mutation. Below the artwork I have included a key that explains who all the people are in the picture with the carriers of the haemophilia mutation in red.

This artwork is designed to be viewed both closeup - to reveal the DNA sequence, and far away - to reveal the image. The closeup that you can see below reveals some important details. The origin of the sequence (bases 1 to 8000) is shown in the bottom right corner - human genome version 38 - chromosome X - from base 139536139 to 139544138 - the SNP rs398122990 (an A to G change at position 139541073 on chromosome X) is located at peak number 4935 of the sequence. It changes a base in intron 3 of the F9 gene transcript. The Human Genome Variation Society (HGVS) notation for this variant is NM_000133.3:c.278-3A>G. As with most of my SangerArtworks I have used the bases after 8000 to sign and date the artwork with a hidden “Sangerism”.

So how does the rs398122990 SNP in the F9 gene cause haemophilia? Well the single base change is close to the 3’ splice site of intron 3 (c.278-3A>G aka IVS3-3A>G), it creates a cryptic splice site, resulting in a frameshift and a prematurely truncated factor IX protein. This shortened factor IX protein does not function properly in the all important cascade of events that control the blood clotting process.

Interesting it is thought that this SNP has probably died out and is no longer present in the gene pool. It reaked havoc in the Royal families of Europe during the 19th and 20th centuries, affecting a total of 9 male descendents of Queen Victoria, but as far as we know it no longer exists - no Royal haemophiliacs have been born since 1914.

You can purchase this artwork in a number of different formats from Society6 or Redbubble using the links below.



Royal Blood - annotations_2000px.jpg
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