Gene mutation and sickle cell

3. Gene mutation and sickle cell (k) explain the effect of the gene mutation resulting in sickle cell anaemia on the structure and oxygen transport efficiency of haemoglobin; (l) outline how DNA is repaired; (m) outline the role of DNA in the process of cellular ageing;

4. Your task • Get into pairs • Read your allocated section from pages 156-157 • Make notes in any form you wish (you have 20 minutes to do this) • One person from each group should join up with one person from each of the two other groups to make a three. • You will then teach each other your section and share notes so that everyone has a completed note. • In your groups of three, complete question 2 from page 193 • Collect the past paper question to work through in your groups. • Once you have completed it, swap with someone from the other group to peer mark. Mark scheme will be provided

5. Sickle cell anaemia and the effect on haemoglobin

6. Sickle cell anaemia and the effect on haemoglobin • At low pO2, haemoglobin forms long, sharp crystals that make RBCs become sickle-shaped and then rupture. • RBCs carry less oxygen, block capillaries and can lead to hypoxia

7. Hypoxia • When oxygen in the blood falls to very low levels • This results in a reduction in cellular oxidation and a reduction in ATP synthesis and, as a result, depressed aerobic activity.

8. How does sickle cell anaemia occur? • Single base substitution in the RNA sequence that codes for the beta chain of haemoglobin. • This results in a different amino acid being produced – valine instead of glutamate. • This type of mutation in the DNA sequence is called a point mutation. • Consequently, haemoglobin now has different properties than before – it becomes less soluble at low oxygen concentrations (low pO2)

9. How does sickle cell anaemia occur?

10. Long chains form due to the amino acid valine being synthesised instead of glutamate in beta haemoglobin.

11. How DNA is repaired • Most mutations occur during DNA replication (when DNA is copied) • Mistakes happen once every 10 genes (roughly) • Changes can occur due to: • Cellular metabolism • UV light exposure • Ionising radiation • Chemical exposure • Replication errors • Normally, these mistakes are corrected by a proof reading mechanism. DNA polymerase does this job. • Once replication of DNA is complete, another group of proteins “surveys” the DNA looking for mismatches in base pairs

12. How DNA is repaired • A form of colon cancer arises because of the inability of DNA “mismatching” to be repaired. • When DNA is damaged, another group of enzymes excise the misparing nucleotides and DNA polymerases and DNA ligases repair the cut strands. • Xeroderma pigmentosum is an example of a disease where DNA damage, due to exposure to UV light, is not corrected. The result is that even low level exposure to UV light can lead to development of skin cancers.

13. Telomeres are found at the end of chromosomes. Their function is to: Protect genes on chromosomes Regulate division of the cell When the cell divides, telomeres are not copied. As a result, they get shorter each time. When they get too short, essential parts of DNA can be destroyed. If telomeres are removed completely, genes become exposed and are easily damaged and mutated. DNA and cellular damage

15. DNA and cellular damage • Telomere length governs how many times a cell can replicate – usually 20-30 times before telomeres become too short. • This is why cells do not last an entire lifetime. • Bone marrow and embryonic stem cells are constantly dividing. They are able to do this and maintain their telomeres by use of the enzyme telomerase. • Most somatic (body) cells do not express this enzyme, although it is found in human cancer cells.