Week 12 - DNA Mutagenesis and Repair Flashcards
What is a mutation?
A direct altercation of a gene resulting in a new allele of that gene
Germline and Somatic Mutations
Germline - occur in cells that produce gametes - affects offspring of individual Somatic - occur in somatic cells - only affect individual - degree of effect is linked to stage of development mutation occurs
Classes of Mutations and the type of mutations that can occur
Point Mutation - substitution - insertion - deletion Chromosomal Mutation - inversion - deletion - duplication - translocation
Types of substitution point mutations
Silent - doesn’t change an amino acid but can still have phenotypic effect
Missense - change amino acid to another amino acid
Nonsense - change amino acid to stop codon
What is a Frameshift mutation?
Insertion point mutation
Deletion or insertion of a number of bases that isn’t multiple of 3
Introduces premature stop codons
Forward and Reverse Mutations
Forward - loss of wild-type allele
Reverse - restores wild-type allele
Phenotypic Effects of Mutations
Loss of function mutation - partial or total loss of functional gene product - recessive, a diploid organism has to be homozygous for this change before the loss of protein is seen phentoypically - e.g. cystic fibrosis Gain of function mutation - creation of a new trait - hyperactivation of the protein - often dominant - e.g. achondroplasia
Suppressor Mutation
Mutation that hides or suppresses the effect of another mutation
Intragenic
- within same gene as original mutation
- can restore a reading frame
Intergenic
- in a different gene to original mutation
- can restore ability of gene to interact
Spontaneous Mutations - Incorrect base pairing
When a mismatched base is incorporated it will produce an error (Wobble)
When strand replicates this error is passed on creating permanent mutation
Spontaneous Mutation - Strand Slipping
One strand forms loop
Base that is looped out isn’t read
Causes different strand to be produced
Strand replicated and mutation passed on
Spontaneous Chemical Changes
Depurination
- loss of a purine base from a nucleotide in a DNA strand
- covalent bond breaks between purine and 1’ C on deoxyribose sugar
- forms apurinic site = no template base during replication
- base randomly added
Deamination
- loss of an amino group from a nitrogenous base
- e.g. cytosine to uracil
- in next round of replication, uracil pairs with adenine
- next round adenine pair with thymine
- gone from C-G to U-A to A-T
Types of Chemically Induced Mutations
Base analogues Deamination Addition of OH groups Alkylating agents Oxidation Intercalating agents
Chemically Induced Mutations - Base Analogues
Similar to real bases e.g. 5 bromo-uracil is uracil with 5’ methyl group swapped for Br
Can from non-standard base pairs
E.g. initially binds to adenine, mispairs with guanine next replication guanine not meant to be there binds with cytosine forming mutation
U-A to C-G
Chemically Induced Mutations - Addition of Hydroxyl groups
Hydroxylamine adds OH group to cytosine
Forms hydroxylaminocytosine which binds to adenine
C-G to A-T
Chemically Induced Mutations - Alkylating agents
Add methyl or ethyl to nucleotides
