9-mutation.ppt

NEW CHAPTER DNA Damage 1 * Learning objectives - Types of DNA damage encounters the DNA. - Types of point mutation. - Frame shift mutation. 2 • DNA damage also know as lesion is an alteration to the chemical structure of one of the components of DNA. It can be single-strand damage and double-...

NEW CHAPTER DNA Damage 1 * Learning objectives - Types of DNA damage encounters the DNA. - Types of point mutation. - Frame shift mutation. 2 • DNA damage also know as lesion is an alteration to the chemical structure of one of the components of DNA. It can be single-strand damage and double-strand damage (Slide 4). • Factors causing DNA damage (lesion) are: 1) environmental : UV light, radon gas 2) contamination : aflatoxin 3) accidental : chemical 4) extreme : cancer chemotherapy drugs 5) endogenous : oxidative metabolism & replication errors 3 Types of DNA damage (lesion) * Repair of damaged DNA (lesion) is done by two ways: Direct repair and Excision repair 4 Mutation 5 • • • Mutation is any alteration to the genetic material (DNA or RNA) that produces heritable change in the nucleotide sequences. Mutagens are chemicals or physical agents that cause damage/lesion to the genetic material. They are two ways in which DNA can become mutated: 1- Mutations can be inherited parent to child 2- Mutations can be acquired Environmental damage, mistakes when DNA is copied (replication errors) 6 Point mutation A type of mutation (localised) that results in the substitution of one base pair for a different base pair These can be of two types: 1- Transition mutation, 2- Transversion mutation - transition mutations are generated at higher frequency than transversions. 7 1) Transition mutation • A transition is a point mutation that substitutes a purine for a purine, and a pyrimidine for a pyrimidine. Transitions can be caused by oxidative deamination and tautomerization. 2) Transversion mutation • A transversion is a point mutation that substitutes a purine for a pyrimidine, and a pyrimidine for a purine. 8 C & T = Pyrimidines G & A = Purines Transition (α) and Transversions (β) 9 * The outcome of point mutation: Polymorphis m 10 * The Codon Table (mRNA) 11 Sickle-cell Anemia Sickle-cell anaemia is caused by a point mutation in the β-globin chain of normal hemoglobin, causing the hydrophilic amino acid glutamic acid (E) to be replaced with the hydrophobic amino acid valine (V) as a result sickle cell hemoglobin (HbS) is formed. DNA 12 Frame Shift Mutation A type of mutation (localised) that results in the deletion or insertion of a nucleotide. Normal DNA frame 13 Gene mutation and Biotechnology 14 • Understanding what is gene mutation and its types is going to help in: 1)Choosing the best biotech approach in treating a disease (ex. Gene therapy) (slide 18) 2)Protein engineering of recombinant protein to produce stable and effective biopharmaceutical product (will be discussed later in the course). 15 Cystic Fibrosis The mutation type in Cystic Fibrosis Transmembrane Regulator (CFTR) gene; deletion of a codon (3 nucleotides) (right) (above) The location of CFTR gene and its function in normal conditions * http://www.hopkinscf.org/what-is-cf/basic-science/cftr/ 16 Learning outcomes • There are many factors can cause DNA damage. The lesion in the DNA can be fixed by the cell instantly to prevent mutation and development of a disorder. • Point mutation and frame shift are most common types of mutation. • Understanding mutation mechanisms can help in better utilize biotechnology techniques to solve disorders associated to mutation. 17