The genetics behind it is due to an amino-acid substitution in the gene coding for the beta-globin of the affected allele.

I’ll like to point out that genes as you said are made up of nucleotides and so you can’t have an amino acid substitution in a gene

However, sickle cell anemia occurs as a result of a single nucleotide mutation (A replaced by T) in the beta globulin gene resulting in the substitution of glutamate by valine at position 6 in the beta globin chain.

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