Mendelian Disorders – Sickle-cell Anaemia

Sickle cell anaemia is an autosomal recessive disorder caused by a point mutation (GAG to GUG) that replaces glutamic acid with valine at the sixth position of the $\beta$-globin chain.
Homozygotes ($Hb^SHb^S$) suffer from severe anaemia. Heterozygotes ($Hb^AHb^S$, sickle cell trait) are mostly healthy.
The malarial parasite Plasmodium falciparum, spread by the Anopheles mosquito, cannot multiply well in red cells containing HbS, which sickle and are removed when infected. So heterozygotes are resistant to malaria.
This is why the sickle cell allele is common in malaria-prone regions such as tropical Africa (balanced polymorphism).
So sickle cell anaemia, though harmful, is a potential saviour from malaria.

Haemoglobin has two $\alpha$ and two $\beta$ polypeptide chains.
In sickle cell anaemia, a point mutation in the $\beta$-globin gene (GAG $\rightarrow$ GUG in the codon) replaces glutamic acid by valine at the sixth position of the $\beta$ chain.
The resulting HbS polymerises at low oxygen, making the RBCs sickle shaped.
So sickle cell anaemia is due to change of an amino acid in the $\beta$-chain of haemoglobin.