The Genetic Basis of Disease

The genetic basis of disease; specifically relating to Sickle Cell Disease.

Sickle cell anaemia affects the structure of the protein haemoglobin. Sickle cell haemoglobin has a decreased affinity for oxygen at low partial pressures of O2. This is brought about by the mutation of the Beta-globin gene, which results in a substitution of an amino acid, altering the original primary structure of the normal functioning haemoglobin. The substitution replaces Valine for Glutamic acid (Hoffbrand et al., 2009), the result of this single amino acid substitution affects the entire properties of the polymerized chain and haemoglobin structure. The subsequent haemoglobin is then faulty, not able to function efficiently as it is unable to transport the required oxygen to respiring cells, resulting in severe complications for the sufferer.

For a genetic trait to be inherited the individual must have at least one of the coding alleles present within their genome. Depending on the nature of the alleles inherited determines whether the trait will be expressed in the phenotype of the individual. In the case of Sickle Cell Anaemia, the most common form of sickle cell disease, it will only become exhibited in the phenotype of people who have acquired two recessive alleles for SCD. However, if only one faulty allele is inherited then the SCD will not be present in the phenotype, although this gene will still appear in the genotype. Therefore this individual is able to pass on the recessive gene responsible for SCD to the next generation. In situations where it is known that both parents are carriers, it would be beneficial to carry out genetic screening of embryos, due to the increase of chance that the offspring would have the sickle cell phenotype. This would prevent the offspring from inheriting the abnormal allele and possibly passing it on to future generations.

Having only one SCD recessive allele within a genotype is known as sickle cell trait, without the Sickle Cell...