Sickle cell anaemia is a non-infectious chronic disease. If not treated, sickle cell anaemia can be painful and life-threatening. Sickle cell anaemia is caused by a base substitution mutation in the gene coding for the ẞ-globin polypeptide of haemoglobin. This leads to a change in the primary structure of the polypeptide, as valine is present instead of glutamine. This results in abnormal sickle-shaped red blood cells, which stick together in blood vessels. Symptoms of sickle cell anaemia include painful attacks when red blood cells block capillaries in tissues and organs.

1. (a)Suggest the consequences to cells when sickle-shaped red blood cells block capillaries in tissues and organs.[2]
2. (b)(i)Outline two advantages of genetic screening for sickle cell anaemia and SCT.[2]
3. (b)(ii)To test for the presence of HbS, DNA is extracted and the polymerase chain reaction (PCR) is carried out with two specific primers. One mutation to produce Hbs is a base substitution in the sixth codon of the ẞ-globin gene. The normal codon GAG changes to GTG. The normal-specific primer detects GAG whereas the mutant-specific primer detects GTG. Explain: • why primers are used in PCR • how the use of two specific primers allows the amplification of the normal, sickle cell anaemia and SCT genotypes.[3]
4. (b)(iii)Gel electrophoresis is carried out on the products of the PCRs. Fig. 4.1 includes the results for two individuals, A and B, tested for the sickle cell allele. • Each lane has an 860 base pair (bp) band to indicate the test is valid. • Lane 1 is a control lane with a 207bp band for an individual with known normal phenotype. • Lane 2 is a control lane with a 207bp band for an individual with known sickle cell anaemia phenotype. • Lanes 1, 3 and 5 contain DNA from the PCR that used normal-specific primer. • Lanes 2, 4 and 6 contain DNA from the PCR that used mutant-specific primer. [Figure 4.1] Deduce the genotypes and phenotypes of individuals A and B in Fig. 4.1. A B[2]
5. (c)(i)The number of cases of sickle cell anaemia is highest in sub-Saharan Africa, the Middle East and India. These areas also have a high incidence of malaria. People with SCT (heterozygotes) are either unaffected or may have mild symptoms of sickle cell anaemia. One advantage of SCT is an increased resistance to malaria. Explain how natural selection operates to maintain the presence of the sickle cell allele in populations in areas with malaria.[4]
6. (c)(ii)Parents who use IVF to produce embryos may decide to have embryos genetically screened by a test known as pre-implantation genetic diagnosis (PGD). Only embryos that do not have sickle cell alleles are transferred to the woman's uterus. Discuss two ethical reasons why parents using IVF may choose not to have PGD.[2]

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