HUMAN GENETIC DISORDERS PART 2 – DIAGNOSIS AND TREATMENT

Abstract

The first genetic test was run in 1978 by Kan and Dozy and independently by Orkin et al. The molecular testing was performed to detect the mutation c.20A>T in the β-globin DNA responsible for sickle cell anaemia. Kan and Dozy applied restriction analysis of the β-globin gene followed by hybridisation with a molecular probe complementary to the fragment of human β-globin sequence (RFLP method) [1]. Results enabled them the discrimination between mutant homozygotes (affected persons), normal homozygotes (healthy persons) and heterozygotes (mutation carriers). To detect the same mutation, Orkin et al. applied hybridisation with two variant oligonucleotide molecular probes to distinguish between mutant and normal alleles of the β-globin gene [2]. A milestone in development of molecular diagnostic techniques for detection of human mutations was the invention of polymerase chain reaction (PCR) made in 1983 by Kary Mullis. The PCR in molecular diagnostics is generally used to amplify DNA fragment before other molecular analyses are performed. Genetic testing is divided in two categories: direct testing and indirect testing (gene tracking). Direct genetic testing involves testing for a certain genotype, i.e. identification of a specific pathogenic mutation within a gene, that is responsible for a certain condition. Indirect genetic testing also known as gene tracking tests the inheritance and segregation of genetic markers linked to a specific condition within a family.