The mutation for sickle cell hemoglobin occurs at which codon(s) in the beta-hemoglobin gene?

• A. the 1st codon after AUG
• B. the 3rd codon
• C. the 6th codon after AUG or the 7th codon of the entire beta-hemoglobin gene
• D. the 12th codon

Answer: (C)

Sickle cell disease stems from a single-nucleotide change in the beta-globin gene that alters one amino acid in the beta-globin protein. The mutation targets the codon for the sixth amino acid after the start codon (AUG). The normal codon for glutamic acid is GAG; a single base change converts it to GTG (or in mRNA, GAG to GUG), which codes for valine. That one amino acid substitution causes hemoglobin S to polymerize when oxygen is low, twisting red blood cells into a sickle shape. If you include the start codon in counting, this sits at the seventh codon, but if you count only the mature protein sequence, it’s the sixth amino acid’s codon. That specific position is why only that codon region fits this mutation.