Mutations and Genetic Disorders

1. Mutations and Genetic Disorders

2. Mutations • “Changes in the DNA sequence that are inherited” • Can have a • negative consequence, • no consequence, or • a positive consequence

3. Types of Mutation POINT MUTATION • Silent Mutations • Base pair substitution Mutations • Mis-sense • Non-sense 3. Frame Shift Mutations • Deletion • Insertion CHROMOSOMAL MUTATION

4. 1.Silent Mutations • Has no consequence (neither good nor bad) • Can happen in 2 ways: • A mutation occurs in an intron, which is spliced out during mRNA processing. • A mutation occurs in the DNA which does not change the amino acid

5. Silent Mutations - Example Example (No change in aa) 5’ – AUG AAG UUU GGC UAA – 3’ Met Lys Phe Gly Stop 5’ – AUG AAG UUU GGU UAA – 3’ Met Lys Phe Gly Stop Original (normal) mRNA Mutated (Base C changed to U) mRNA But no change in amino acid

6. 2. a Missense Mutations • A change in a nitrogenous base leads to a change in the amino acid produced. Ex. Sickle Cell Anemia 5’ – AUG AAG UUU GGC UAA – 3’ Met Lys Phe Gly Stop 5’ – AUG AAG UUU AGC UAA – 3’ Met Lys Phe Ser Stop Original (normal) mRNA Missense mutation (G base changed to A) = A different amino acid

7. 2. B Nonsense Mutations • A change in a nitrogenous base leads to a premature stop codon 5’ – AUG AAG UUU GGC UAA – 3’ Met Lys Phe Gly Stop 5’ – AUG UAG UUU GGC UAA – 3’ Met Stop Original (normal) mRNA Nonsense mutation (A base changed to U) = Premature stop codon

8. Classification • Missense and Nonsense mutations arise because of a base pair substitution • In other words, the nitrogenous base itself may change, but the number of nitrogenous bases don’t change

9. 3. A Deletion Mutations • One or more bases are deleted 5’ – AUG AAG UUU GGC UAA – 3’ Met Lys PheGly Stop 5’ – AUG AAG UUG GCU AA – 3’ Met Lys LeuAla Original (normal) mRNA Deletion of the base “U” = The “reading frame” shifts, and new amino acids result

10. 3. B Insertion Mutations • The addition of one or more bases 5’ – AUG AAG UUU GGC UAA – 3’ Met Lys Phe Gly Stop 5’ – AUG UAA GUU UGG CUA – 3’ Met Stop Original (normal) mRNA Insertion of the base “U” = The “reading frame” shifts, and a stop codon results. This frameshift insertion cause a nonsense mutation

11. Classification • Frameshift mutations occur because of insertions or deletions • NOTE: All of these mutations (missense, nonsense, insertions, deletions) are called point mutations meaning that they occur only with one base pair

12. Classification • Another category of mutations involves large segments of DNA • These are called chromosomal mutations TRANSLOCATIONS INVERSIONS

13. How do mutations arise? • What causes mutations? • List examples • Spontaneously • Mutagenic agents (chemicals that cause mutations, e.g. X rays, UV radiation, cosmic rays, chemicals)

14. Try It! The following strand of mRNA represents the “normal” (aka wild type) strand. 5’ – AUG GGG UUU AUC CUA UAG – 3’ This strand is hit by UV radiation and turns into: 5’ – AUG GGG UUG AUC CUA UAG – 3’ • Write the amino acid sequences for both strands • What kind of mutation occurred? Be very specific. • What would happen if the “UUG” changed into “UAG”?

15. Home Work • Pg # 263 , Q # 1 to 7