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DNA Mutations and Repair
Chapter 17
Mutation: is defined as an inherited change in genetic information by cell division or individual organisms.
Chernobyl, April 26th, 1986
Mutations can be classified into categories.
Categories of mutationsCategories of mutations
Somatic and germ line
Achondroplasia
Autosomal Dominant
Gene Mutations can also be classified by type of mutation
1. Base Substitutions
□ 2. Insertions and deletions
3. Frameshift mutations
4. Expanding trinuleotide repeats
Lead to
Gene Mutations can also be classified by type of mutation
Base Substitutions
Transitions and Transversions
can be
PURINE TO PURINEPURINE TO PYRIMIDINE
PYRIMIDINE TO PURINE
Expanding trinucleotide repeats
Fragile X Syndrome
Pre-mutation
Fragile X syndrome:FMR-1 gene
Strand slippage may cause repeats
Phenotypic changes and mutations
Reverse mutationForward mutation
Forward versus Reverse Mutations
Terms associated with PHENOTYPIC effects of mutations on protein structure
Phenotypic effects can also change function
1 Sullivan, J.P. et al., Department of Pathology, College of Veterinary Medicine, 1998 The University of Georgia, Athens, GA
Gain of Gene Function1
Loss of Gene Function2
Qualtek Molecularlabs Web Site
or
Loss of Function can also occur!
Typically recessive mutations!
Suppressor Mutations is a genetic change that hides the effect of another mutation
Intragenic Suppressor Mutations
Intergenic Mutation
Lethal Mutations
Do you remember something about each type of mutation?
This is easy!
Mutation Rates and Frequency
1 to 10 mutations per million gametes Incidence within a group
Causes of Mutations
Spontaneous Induced
Environmentally Induced DNA changes
Intercalating agents Insert and distort DNA
Radiation
Hiroshima (Aug. 6th, 1945) (Techa River)
Thymine DimersSOS
Chemicals and Reactions Leading to Mutations
alklyating
Deamination
Adds OH
Oxidative radicals Reactive forms of
oxygen can lead to these radicals
Detecting mutations with the AMES test
THE AMES TESTSalmonella typimurium
AMES TEST Saccharin
Aflatoxin
2-aminofluorene
Aflatoxin B1
DNA Repair: general characteristics Double stranded DNA Redundancy of pathways
Types of DNA repair Mismatch repair
Direct Repair
Base-Excision Repair
Nucleotide Excision Repair
Mismatch repair Mut H
Recognize GATC hemi-methylation
Mut S Mut L
A closer look at mismatch repair
Direct Repair
DIRECT REVERSAL REPAIR
BASE EXCISION REPAIR
BASE EXCISION REPAIR
Nucleotide Excision Repair
Diseases of DNA repair!
Xeroderma pigmentosumAutosomal recessive
Hereditary Non-Polyposis Colon Cancer
HNPCC
15% of all colon cancers
Li-Fraumeni P-53 mutation
The End