These are disorders of haemoglobin. Haemoglobin is a red coloured protein found within red blood cells. It is composed of two basic parts - the pigment haem (which contains iron) and the protein globin. Variants of the globin protein cause the haemoglobin disorders. The main function of haemoglobin is taking up oxygen in the lungs, transporting it around the body in red blood cells and releasing it in the tissues.
Adult haemoglobin (haemoglobin A) is a complex protein that consists of two alpha and two beta globin chains (a2ß2). Separate genes control the production of the alpha and beta globin chains.
Variants of these genes usually have one of two effects. Some alter the structure of a globin chain, leading to production of a normal amount of an unusual haemoglobin. These are called structural haemoglobin variants (such as haemoglobin S associated with sickle cell anaemia). Others reduce or abolish production of a globin chain. These are called thalassaemias. To see common examples of the four main categories of haemoglobin gene variants, go to Supplementary Information.
The sickle cell diseases are defined by the presence of haemoglobin S in the red blood cells. They are associated with variants of the beta globin (HBB) gene which is located on chromosome 11. Sickle cell anaemia is the commonest disease in the group, but other forms of sickle cell diseases result from inheriting haemoglobin S and other beta-globin variants (such as haemoglobin C or beta thalassaemia.)
Alpha-thalassaemia is caused by alpha globin gene variants which reduce the production of alpha globin chains.
Beta-thalassaemia is caused by beta globin gene variants which reduce or abolish production of the beta chain.
Cystic fibrosis is caused by variants of the CFTR gene located on chromosome 7. The CFTR gene codes for a protein that is found in various cell types, including lung epithelium, submucosal glands, pancreas, liver, sweat ducts and reproductive tract.
CFTR is involved in regulating the transport of chloride and sodium through the cell membrane. When chloride transport is altered because of impaired CFTR function, the flow of water across the cell membrane is also affected. This causes the accumulation of thick, viscid secretions in the lumen of organs lined by epithelium, particularly the lungs.