DNA Mutations and Repair Chapter 18 Part 1

Gene Mutations and Repair  Nature of mutations  Causes of mutations  Study of mutations  DNA repair

Chernobyl, April 26 th, 1986 Source of Mutations Nuclear accidents

Source of Mutations Japan’s Tsunami disabled reactors at the Fukushima Plant March 11, 2001

Mutation: is defined as an inherited change in genetic information by cell division or individual organisms.

Mutations can be classified into categories. Categories 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 PURINE PURINE TO PYRIMIDINE PYRIMIDINE TO PURINE

Expanding trinucleotide repeats

Fragile X Syndrome Pre-mutation

Fragile X syndrome:FMR-1 gene

Update on diagnosis of fragile X Syndrome: Fragile X syndrome was originally diagnosed by culturing cells in a folate deficient medium and then assessing the cultures for X-chromosome breakage by cytogenetic analysis of the long arm of the X- chromosome. This technique proved unreliable for both diagnosis and carrier testing. cytogenetic The fragile X abnormality is now directly determined by analysis of the number of CGG repeats and their methylation status using: restriction endonucleaserestriction endonuclease digestion and Southern blot analysis.Southern blot

Strand slippage may cause repeats

Phenotypic changes and mutations

Spontaneous: slippage

Reverse mutation Forward 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 Function 1 Loss of Gene Function 2 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?