Genetics of haemochromatosis Inherited (genetic) disorders are caused by defective genes in the cells which make up the body. Genes are made of DNA and contain the information the body needs to develop from the egg and to maintain itself in good working order. We have about 30,000 genes and every cell in the body, except sperm and egg cells, contains two copies of each. One of these copies is inherited from our mother and one from our father. In 1996 the HFE gene was identified as the major gene implicated in haemochromatosis. The genetics of GH A small change (mutation) is present in both copies of the gene in over 90% of those diagnosed with GH. GH is an autosomal recessive disorder, which means that the risk of absorbing excess iron is higher if both copies of the gene are abnormal. Someone with only one copy of a mutation rather than two is said to be a carrier. If only one copy is defective, an individual will usually be unaffected, but it is known that carriers. Some carriers are known to load iron, sometimes. A carrier is able to pass on his or her abnormal copy of the gene to a son or daughter. Sperm and egg cells have only one copy of each gene, and on average half the eggs or half the sperm of a carrier will contain the defective version. By contrast, all the eggs or sperm of an individual in whom both gene copies are defective – and who, as a result, has haemochromatosis – will carry the abnormal gene. To develop GH you have to inherit a defective gene or genes from your parents. This can happen in three ways. 1. If both parents are carriers This is the most common situation. On average a quarter of resulting children will develop GH, half will be carriers, and a quarter will be unaffected (clear). 2. One parent has GH and the other is a carrier This occurs in about 1 in 2000 partnerships. On average half of all children will develop GH, the other half will be carriers. 3. If both parents have GH This is a rare event, occurring in about 1 in 100,000 partnerships. In this situation all children will definitely inherit two defective genes – one from each parent – and will therefore also have GH. It should be emphasised that the proportions cited above are averages for the whole population. Thus, for example, in any particular family where both parents are carriers (scenario 1 above) it is possible for all children to be affected, all to be carriers, or for all to be clear. How recessive inheritance works when both parents are carriers (scenario 1) is also shown in this diagram: In the light of this relatives of someone who has been diagnosed and who are at risk should be tested. This is particularly important in the case of brothers and sisters (siblings) as they stand at least a 1 in 4 chance of being affected. Parents, partners and children, should also be tested. The Celtic link GH is sometimes described as The Celtic Curse. Although this is not a particularly attractive phrase, it does underscore the fact that those people with Celtic ancestry are far more likely to be affected. Many people with GH can immediately identify Celtic family roots. However it is important to understand that the condition can affect people of all ethnicities, it is just more prevalent in people with Celtic roots. Thus there are much higher rates of GH in Scotland, Northern Ireland (especially), the North-West of England, Republic of Ireland, Northern France and Northern Spain than elsewhere. The same applies to other parts of the world to where people from these areas subsequently migrated. This map, from a 2016 study conducted in the US, shows the prevalence of genetic haemochromatosis across Europe. The dark red areas indicate high prevalence where relatively more people have the condition. The blue areas represent low prevalence.