Chapter 17. Gene Mutations and DNA Repair (Part 1) What does this tell us?

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1 Chapter 17 Gene Mutations and DNA Repair (Part 1) What does this tell us? 1

2 What does this tell us? Mutations will confer upon us a wide variety of super powers What does this tell us? Mutations will confer upon us a wide variety of super powers. Barrie is a nerd. Who Cares? Mutations are the Ultimate Source of Genetic Variation. Mutations are the Source of Many Human Disorders. Mutation: A HERITABLE change in genetic information. Mutations are invaluable tools for Studying Genetics. Genetic Dissection Break Component Parts Effect on Phenotype? Common in Developmental Biology Zebrafish Developmental Mutants 2

3 Know This! Called a Mosaic.? Know This! Figure 17.2 Do we care about Somatic Mutations? Some Somatic Mutations: Increase rates of cell division These cells increase in number and spread These cells have a selective advantage This is the basis of all CANCERS I knew that! So What? 3 Basic Types of Mutation Figure 17.2 Base Substitutions Transition: Purine to purine, Pyrimidine to pyrimidine Transversion: Purine to Pyrimidine, Pyrimidine to Purine Single base is changed Insertion Addition of one or more nucleotides Deletion Removal of one or more nucleotides 3

4 FrameShift Mutations = Bad Caused by Insertions or Deletions in protein coding loci. In-Frame Mutations = Not as Bad Some Insertions and Deletions may leave the reading frame intact 3 AAA TCA CTT GGC GTA CAA GTG ATC GGC TCT 5 Phe Ser Glu Pro His Val Gln Stop 3 AAA TCA CTT GGC GTA CAA GTG ATC GGC TCT 5 3 AAA TCA CTT GGG TAC AAG TGA TCG GCT CT 5 Phe Ser Glu Pro Met Phe Thr Ser Arg. 3 AAA TCA CTT GGC GTA CAA GTG ATC GGC TCT 5 Phe Ser Glu Pro His Val Gln Stop 3 AAA TCA CTT GGC GTA CAA GTG ATC GGC TCT 5 3 AAA TCA CTT GGA CAA GTG ATC GGC TCT 5 Phe Ser Glu Pro Val Gln Stop Protein is mostly the same, but mutation may still have an effect t on phenotype Expanding Trinucleotide Repeats Copies of a trinucleotide increase in numbers Number of repeats proportional to age of onset and severity of disease Anticipation: Disease gets worse with each generation Examples: Huntington s Disease, Fragile X Syndrome, others (Table 17.1) Phenotypic Effects of Mutations Forward Mutation: Changes the wild type to mutant Reverse Mutation: Changes the mutant to wild type Phenotypic Effects of Mutations Missense Mutation: Base substitution that alters a codon, resulting in a different amino acid in the protein. Nonsense Mutation: Changes sense codon into stop codon. Silent Mutation: Alters codon to a synonymous codon Neutral Mutation: Amino acid sequence changed, but little influence on protein function. 4

5 Figure 17.7 Phenotypic Effects of Mutations Loss of Function: Protein structure altered, no longer works. Gain of Function: Produces an entirely new trait, or causes trait to appear in a new place or at a new time Conditional: expressed only under certain conditions Lethal: Death Suppressor Mutations Suppresses the effect of another mutation Intragenic suppressor: within the same gene as original mutation Intergenic suppressor: in a different gene from original mutation What might be some mechanisms for intragenic and intergenic suppression? Figure

6 Studying Mutations: Reversion Can use mutagens to discover the molecular nature of a mutation of interest Frameshift? Transition? Transversion? Studying Mutations: : The Ames Test A bacterial test that identifies potential mutagens his- Salmonella typhimurium plated on media lacking Histidine Increase in bacterial colonies on plate treated with chemical: Potential Mutagen! Figure Figure SPONTANEOUS Reversions! Why colonies in control? 6

7 Figure Wait a minute! What about chemicals that are converted into mutagens in the body? Figure The bacterial his- strains are mixed with liver enzymes. Potential metabolic conversion of the chemical to a mutagen is therefore addressed by the Ames Test. Allright Then! Control Mutagenic? Control Mutagenic? Yes 7

8 Control Mutagenic? Control Mutagenic? Yes Yes No No? Some known carcinogens are NEGATIVE in the Ames Test. Prokaryotes are not a perfect analog to the human body. Other mutation testing models (such as transgenic mice) have therefore been developed. Source: In 1975, researchers using the Ames Test discovered that most hair dyes contained mutagenic compounds. 90% of known carcinogens are also mutagens 8

9 Other AMES Test Results Isoiazid: Positive (drug to prevent TB) Safrole: Positive (Now banned) (flavoring agent in root beer) Aflatoxin: Positive Present in moldy grain and peanuts Saccharin: Negative sweetener On Friday, we will look at the CAUSES of mutations, and how they are REPAIRED. 9

www.lessonplansinc.com Topic: Gene Mutations WS Summary: Students will learn about frame shift mutations and base substitution mutations. Goals & Objectives: Students will be able to demonstrate how mutations

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