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This "DNA dot-to-dot" digital drawing is made from the sequence of the human haemochromatosis gene (homeostatic iron regulator - HFE). Hereditary haemochromatosis is a common genetic condition that affects around 1 in 200 people of European background and leads to iron overload. The "rusty cog", made using the HFE gene sequence, is a metaphor for haemochromatosis - the human body is like a machine, made from lots of moving parts that all need to function for the whole thing to work. When HFE does not function iron builds up in the form of rust, preventing the machine from working properly.

 

Haemochromatosis is characterised by uncontrolled absorption of iron from the diet and its toxic accumulation in many of the body's organs, including the liver, pancreas, joints and heart. Over time this can lead to organ damage, resulting in liver cirrhosis, arthritis, diabetes and heart disease and symptoms such as fatigue, weakness, abdominal pain and aching joints.

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Many people with haemochromatosis find out they have the condition when they have accumulated significant amounts of iron and have developed symptoms. Thankfully, most of the symptoms can be reversed by treatment, which involves the regular donation of blood. Hence knowledge and awareness of the disease are essential for early diagnosis to prevent serious damage from occurring.

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Haemochromatosis is an autosomal recessive condition meaning that you need 2 copies of a defective HFE gene to develop iron overload, one inherited from each parent. In most cases people with haemochromatosis have 2 copies of the p.C282Y mutation. This mutation which is common in northern European populations is due to a single spelling mistake in the HFE gene sequence - a guanine (G) to adenine (A) change at position 845 of the coding sequence, termed c.845G>A. This small mistake leads to a change in the HFE protein sequence - a cysteine (C) to tyrosine (Y) change at position 282 of the protein, termed p.C282Y. This mutant protein does not function as it should. Normally HFE acts like a sensor of iron levels, responding to increased iron in the body by switching off iron absorption. In haemochromatosis this thermostat-like function is lost, and the body will continue to absorb iron even when levels are dangerously high. A second mutation termed c.187C>G, p.H63D is also very common but it only has a small affect on the function of the HFE protein. This means that most people with this minor mutation will not develop iron overload but those with one copy of each mutation, known as p.C282Y/p.H63D compound heterozygotes do sometimes develop iron overload, although usually have less severe disease than p.C282Y homozygotes.