Question

Jacob is genetically a carrier of the disorder that affects the shape of the RBCs, as shown in the diagram below. His son James suffers from the same disorder.

1. Give the biochemical reason for the disorder that changes the shape of the RBCs, as shown above.
2. Draw a Punnett square to show the genotype of the mother of James.
3. Name and define the type of 'point mutation' responsible for this disorder.

Answer 1

1. Red blood cells take on a sickle-like structure when oxygen tension is lowered since the deoxygenated sickle cell haemoglobin (HbS) molecules polymerize to form long fibres.

2. Given Jacob is a carrier, his genotype has to be Hb^A Hb^S.

   James, Jacob's child, suffers with the condition; so, his genotype is Hb^S Hb^S.

   According to the provided data, James must inherit one Hb^S allele from each parent if he is to have sickle call anaemia (Hb^S Hb^S). Given Jacob's known carrier status (Hb^AHb^S), he most certainly passed on the Hb^S gene to James. James's need for two Hb^S alleles requires the mother to have likewise supplied a Hb^S allele. The condition (Hb^S Hb^S) or a carrier (Hb^A Hb^S) can have an impact on the mother.

   Case 1. When mother is a carrier (Hb^A Hb^S)

                      Mother

   	HbA	HbS
   HbA Jacob	HbA HbA (Normal)	HbA HbS (Carrier)
   HbS	HbA HbS [Carrier]	HbS HbS [Sickle cell]

   James will suffer from a disorder.

   Case 2. When mother is affected (Hb^S Hb^S)

                      Mother

   	HbS	HbS
   HbA Jacob	HbA HbS (Carrier)	HbA HbS (Carrier)
   HbS	HbS HbS [Sickle cell]	HbS HbS [Sickle cell]

   James will suffer from a disorder.

3. A monogenetic condition, sickle cell anaemia is caused by a single base-pair point mutation in the β globin gene, substituting glutamic acid for valine in the β-globin chain.