<prompt> Sickling in ;HbS; disease is primarily caused byDecreased solubilityDecreased stabilityAltered functionAltered O2 binding capacity  <response>: sickle-cell disease, which is caused by mutation of a single base out of the 3 x 109 in the genome, a T-to-A DNA substitution, which in turn results in an A-to-U change in the mRNA corresponding to the sixth codon of the b-globin gene. The altered codon specifies a different amino acid valine rather than glutamic acid, and this causes a structural abnormality of the b-globin molecule leading to haemoglobin aggregation and red blood cell sickling..When HbS is deoxygenated, it undergoes a pronounced decrease in solubility 