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1. The difference between the normal hemoglobin protein DNA sequence and the sickle cell hemoglobin DNA sequence is a base to base shift, in this case adenine (GAG) to thymine (GTG).

2. The difference affects the amino acid sequence of the protein by replacing glutamic acid (Glu) with valine (Val).

Explanation:

In sickle cell anemia, a change in the DNA nucleotide sequence is observed, where adenine is substituted by thymine, whose expression is the change in the amino acid sequence of globine β, incorporating valine instead of glutamic acid. This represents a molecular mutation - point mutation - by subtitution, which corresponds to missense mutation.

Normal hemoglobin protein in a RBC

DNA                 CTG ACT CCT GAG GAG AAG TCT

Amino acids     Leu  Thr   Pro   Glu   Glu   Lys   Ser

Sickle cell hemoglobin protein in a RBC

DNA                 CTG ACT CCT GTG GAG AAG TCT

Amino acids     Leu  Thr   Pro   Val   Glu   Lys   Ser

When GAG is transcribed to mRNA, the CUC codon is obtained, which codes for glutamic acid. Thymine substitution causes the DNA sequence to change to GTG, which is transcribed as CAC, the codon that encodes the amino acid valine. The change from glutamic acid to valine in β-globin causes an altered hemoglobin, giving the abnormal erythrocytes observed in sickle cell disease.

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