The order of the genes in the beta-globin cluster is 5' - epsilon – gamma-G – gamma-A – delta – beta - 3'.

Beta thalassemia minor results in a mild microcytic anemia that is often asymptomatic or may cause fatigue and or pale skin.

[13] Beta thalassemia major can be treated by lifelong blood transfusions or bone marrow transplantation.

[14][15] According to a recent study, the stop gain mutation Gln40stop in HBB gene is a common cause of autosomal recessive Beta- thalassemia in Sardinian people (almost exclusive in Sardinia).

As a curiosity, the same mutation was also associated to a decrease in serum LDL levels in carriers, so the authors suggest that is due to the need of cholesterol to regenerate cell membranes.

[22] Another point mutation in HBB, in which glutamic acid is replaced with lysine at position 26 (β26Glu→Lys), leads to the formation of haemoglobin E (HbE).

Even though the unstable protein itself has mild effect, inherited with HbS and thalassemia traits, it turns into a life-threatening form of β-thalassemia.

[24] Malaria due to Plasmodium falciparum is a major selective factor in human evolution.

[26] People of African descent have evolved to have higher rates of the mutant HBB because the heterozygous individuals have a misshaped red blood cell that prevent attacks from malarial parasites.

Thus, HBB mutants are the sources of positive selection in these regions and are important for their long-term survival.