Hereditary hemochromatosis (HH) is one of the most common genetically transmitted conditions in individuals of Northern European ancestry. The disease is characterized by excessive intestinal absorption of dietary iron, resulting in pathologically high iron storage in tissues and organs. If left untreated, HH can damage joints and organs, and eventually lead to death. There are four main classes of HH, as well as five individual molecular subtypes, caused by mutations in five genes, and the approaches implemented in the discovery of each HH type have specific histories and unique aspects. In this chapter, we review the genetics of the different HH types, including the strategies used to detect the causal variants in each case and the manner in which genetic variants were found to affect iron metabolism.
Keywords: Ferroportin 1 (SLC40A1); HFE; Hemochromatosis; Hemojuvelin (HJV); Hepcidin (HAMP); Iron absorption; Iron overload; Linkage mapping; Transferrin receptor 2 (TFR2).