(N/A) The defect 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.
This amino acid substitution in the globin protein occurs due to a single base substitution at the sixth codon of the $\beta$-globin gene,where $GAG$ is replaced by $GUG$.
The mutant hemoglobin molecule undergoes polymerization under low oxygen tension,causing the shape of the $RBC$ to change from a biconcave disc to an elongated,sickle-like structure.
Sickle-shaped red blood cells obstruct capillaries and restrict blood flow to organs,resulting in ischemia,severe pain,tissue necrosis,and often organ damage.