Sickle Cell Anemia and Gene Transfer Explained

Posted on Mar 25, 2025 in Biology

Sickle Cell Anemia: A Genetic Perspective

Sickle cell anemia is a genetic disease that affects the body’s red blood cells. It is caused by a mutation in the Hb gene, which codes for a polypeptide of 146 amino acids, a crucial component of haemoglobin. Haemoglobin is a vital protein in red blood cells responsible for oxygen transport.

In sickle cell anemia, the codon GAG found in the normal Hb gene is mutated to GTG. This is known as a base substitution mutation, where adenine (A) is replaced by thymine (T). Consequently, during transcription, the messenger RNA (mRNA) codon changes. Instead of the normal GAG, the mRNA contains GUG. This alteration leads to an error during translation.

Normally, the GAG codon on the mRNA pairs with the CUC anticodon on the transfer RNA (tRNA) carrying glutamic acid. However, with the mutated gene, GUG on the mRNA pairs with the CAC anticodon on the tRNA, which carries valine. This substitution—glutamic acid being replaced by valine at the sixth position on the polypeptide—results in haemoglobin S instead of the normal haemoglobin A.

This change affects the phenotype: instead of producing normal, donut-shaped red blood cells, some red blood cells become sickle-shaped. These sickle-shaped cells cannot carry oxygen as efficiently. However, there’s a notable advantage: sickle cell red blood cells confer resistance to malaria. Therefore, the HbS allele on the Hb gene, causing sickle cell anemia, is prevalent in regions where malaria is common.

Gene Transfer: Insulin Production and Other Applications

The human gene coding for insulin can be inserted into a plasmid, which is then introduced into a host cell, such as a bacterium. This bacterium can then synthesize insulin, which is collected and used by individuals with diabetes. The process is as follows:

  1. Messenger RNA (mRNA) coding for insulin is extracted from a human pancreatic cell.
  2. DNA copies are made from this mRNA using the enzyme reverse transcriptase.
  3. Additional guanine nucleotides are added to the gene’s ends, creating “sticky ends.”
  4. Simultaneously, a selected plasmid is cut using restriction enzymes at specific base sequences.
  5. Extra cytosine nucleotides are added to create complementary “sticky ends.”
  6. The prepared plasmid and gene are mixed. They link through complementary base pairing (cytosine to guanine).
  7. DNA ligase is used to form the sugar-phosphate bonds.
  8. The plasmids containing the human insulin gene (recombinant plasmids) are mixed with host cells (e.g., bacteria).
  9. The bacteria take up the plasmid and begin producing insulin, which is then collected and purified.

Other Examples of Gene Transfer:

  • The transfer of the gene for factor IX (a blood clotting factor) from humans to sheep, enabling factor IX production in the sheep’s milk.
  • The transfer of a gene conferring resistance to the herbicide glyphosate from bacteria to crops. This allows the crops to be sprayed with the herbicide without being harmed.