3.2 Applications and skills

3.2.1 Sickle cell anemia

  • Red blood cells contain globular proteins called hemoglobin, which are made of two α- and two β- protein subunits.

Figure 3.2.1a – Structure of hemoglobinFigure 3.2.1a – Structure of hemoglobin

Figure 3.2.1b – DNA base substitution affects mRNA and polypeptideFigure 3.2.1b – DNA base substitution affects mRNA and polypeptide

  • When the mutation is transcribed by mRNA, the resulting codon also contains a substitution and when the mRNA is translated, the mutant polypeptide has valine instead of glutamic acid as the sixth amino acid in the polypeptide chain.
  • Valine and glutamic acid have different chemical properties, so the polypeptide folds differently, the hemoglobin molecule differs in configuration and the red blood cell develops into a sickle shape.

Figure 3.2.1c – Sickled red blood cells developFigure 3.2.1c – Sickled red blood cells develop

  • Sickle-shaped red blood cells deliver oxygen inefficiently and their irregular shapes often block blood vessels. A person with the disease may develop severe symptoms of anemia. The disease is deadly when left untreated.

Inheritance of sickle cell anemia

  • Sickle cell anemia is inherited in an autosomal recessive pattern. This means that both copies of the gene must show the sickle cell trait in order to show symptoms of the disease.

Figure 3.2.1d – Inheritance of sickle cell traitFigure 3.2.1d – Inheritance of sickle cell trait

  • Carriers who are heterozygous for the sickle cell trait do not show symptoms of the anemia but do have sickle-shaped red blood cells.
  • In other words, the sickle cell allele is co-dominant with the normal hemoglobin allele since both alleles affect the phenotype (shape of red blood cells).

Malaria and the sickle cell trait

  • Sickle cell anemia is often deadly, yet approximately 40% of people of African descent are carriers of the trait.

Figure 3.2.1e – Geographical distribution of sickle cell allele and malariaFigure 3.2.1e – Geographical distribution of sickle cell allele and malaria

  • The geographical distribution of the sickle cell allele is very well correlated with the incidence of malaria. Malaria is caused by a parasite that is transmitted to the bloodstream by mosquitoes.
  • Numerous studies have shown that carriers of the sickle cell trait have lower counts of the malaria-causing parasite in their bloodstream.

Figure 3.2.1f – Parasite concentration in the blood of normal (Hb AA) and heterozygous (Hb AS) children in southwest Nigeria Figure 3.2.1f – Parasite concentration in the blood of normal (Hb AA) and heterozygous (Hb AS) children in southwest Nigeria 

  • Scientists have long suspected that the sickle cell trait somehow protects infections by the parasite that causes malaria.
  • This hypothesis is known as the ‘heterozygous advantage’. Despite its deadly effects, the sickle cell trait has been maintained in the population because carriers are protected from the harmful effects of another disease.

Figure 3.2.1g – Sickle cellFigure 3.2.1g – Sickle cell
Micrograph of normal red blood cells (right, top and bottom) and a sickle cell (left)

Figure 3.2.1h – MosquitoFigure 3.2.1h – Mosquito
Mosquitoes transmit the parasite Plasmodium, which causes malaria

Figure 3.2.1i – PlasmodiumFigure 3.2.1i – Plasmodium
Plasmodium (brown) infecting red blood cells

TOK

There is a correlation between the prevalence of sickle cell anemia and malaria. How can we determine if there is a causal link?

Figure 3.2.1j – DiversityFigure 3.2.1j – Diversity

International mindedness

Humans have the vast majority of base sequences in common, but there are many single nucleotide polymorphisms that contribute to human diversity.