Which of the following is the primary defect which leads to sickle cell anemia?

Sickle cell anemia is a hereditary hemoglobinopathy characterized by the production of a structurally abnormal hemoglobin. It results from a point mutation that leads to a substitution of valine for glutamic acid at the 6th position of the beta globin chain. The resultant hemoglobin is HbS, which has abnormal physiochemical propeies that lead to sickle cell disease. Ref: Robbins Pathologic Basis of Disease, 6th Edition, Pages 11, 615-9.