Mutations

1. Mutations SBI 4U November 23rd, 2012

2. What are Genetic Mutations? • Changes in the DNA sequence caused by various mechanisms • Mechanisms of change: synthetic chemicals, radiation, incorrect replication, and random mutations • Beneficial vs. harmful

3. Genetic Mutations • Small Scale • Large Scale

4. Small Scale Mutations • Small-scale mutations: mutations of an individual base pair (point mutations) or of small groups of base pairs • 3 types: -substitution -insertion/deletion -inversion

5. Point Mutations Mutations of an individual base pair 3 Types: • Substitution of one base for another • Insertion or deletion of a single base pair • Inversion of two adjoining base pairs Effects of small-scale mutations can range from being positive to none to severe!

6. Small-Scale Mutations Can be functionally divided into 4 categories: • Missense mutations • Nonsense mutations • Silent mutations • Frameshift mutations

7. Missense Mutation • Missense mutation: when a change of a single base pair or group of base pairs results in the code for a difference amino acid • May be non-functional or functional (differently)

8. Missense Mutation • Ex: sickle cell disease • Hemoglobin molecule altered – sickle shape of RBCs • Replacement of A by T – makes valine instead of glutamic acid

9. Nonsense Mutation • Nonsense Mutation: occurs when the change of a single base pair or group of base pairs results in a premature stop code in the gene • Unable to function

10. Nonsense Mutation • Ex: Cystic fibrosis • Only 493 amino acids produced instead of 1480 (in some cases)

11. Silent Mutation • Silent mutation: occurs when the change in one or more base pairs does not affect the functioning of the gene. • Resulting protein  not altered!

12. Frameshift Mutation • Frameshift mutation: occurs when one or more nucleotides are inserted into or deleted from a DNA sequence, causing the reading frame of codons to shift in one direction or the other • Multiple missense and nonsense mutations • Ex: Tay Sachs disease

13. Large-Scale Mutations • Large-scale mutations involve multiple nucleotides, entire genes, or whole regions of chromosomes • Entire coding regions of DNA may be removed – ex: Dystrophin and Duchenne muscular dystrophy

14. Large-Scale Mutations • Chromosomal translocation: entire genes or groups are moved from one chromosome to another • Inversion: reversal of direction in the genome • Trinucleotide repeats  triplet of nucleotides  repeat uncontrollably - - CAG CAGCAGCAGCAG Ex: Huntington’s disease

15. Causes of Mutations • Spontaneous: arise from inaccurate DNA replication • Induced: environmentally caused

16. Induced Mutations • Caused by a mutagen, that directly alters the DNA within a cell • 2 types of mutagens: chemicals and radiation

17. Chemical Mutagens • Any chemical agent that can enter cell nucleus and chemically alter the structure of the DNA • Ex: tobacco smoke and exhaust fumes

18. Chemical Mutagens • How do they cause mutations? Some mimic a DNA nucleotide. Ex: ethidium bromide  inserts itself between the strands of the double helix and alters structure of DNA

19. Radiation • Lower energy radiation such as ultraviolet B can cause bonds to form between adjacent nucleotides – making a kink - - ex: skin cancer • Higher energy radiation – breaks bonds within the DNA molecule  re-arrangement or deletion of large portions of chromosomes. Ex: x-rays can lead to tumours