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 26th, 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 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

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.

The fragile X abnormality is now directly determined by analysis of the number of CGG repeats and their methylation status using: restriction endonuclease digestion and Southern blot analysis.

Strand slippage may cause repeats

Phenotypic changes and mutations

Spontaneous: slippage

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?