It is an autosome-linked recessive trait that can be transmitted from parents to the offsprings when both the partners are the carrier for the gene (heterozygous).
The disease is controlled by a single pair of alleles, HbA and HbS.
Out of the three possible genotypes only homozygous individuals for HbS (HbSHbS) show the diseased phenotype.
It is caused by the substitution of glutamic acid (Glu) by valine (Val) at the sixth position of the beta-globin chain of the hemoglobin molecule.
The mutant hemoglobin molecule undergoes polymerization under low oxygen tension causing the change in the shape of the RBC from biconcave disc to the elongated sickle-like structure.