Mutations Pt 1 Flashcards
Define Mutation
Any alteration to the genetic material (DNA/RNA) that produces a heritable change in the nucleotide sequence
Name the 3 types of large scale global mutations
- Chromosomal aberrations
- Genome rearrangements: redistribution of genetic material between non-homologous chromosomes
- Change is chromosome number (aneuploidy): e.g. trisomy resulting in Down’s syndrome
Name the 4 types of large scale chromodomal aberrations
- Deletions
- Duplications
- Insertions
- Inversions
What is a point mutation
single nucleotide change
e.g. base substitution or loss/gain of a single nucleotide
What is a deletion/insertion mutation
Loss or gain of bases
What is a duplication mutation
A sequence is repeated
What is an inversion mutation
A sequence within the DNA is inverted
What is a translocation/transposition mutation
Movement of a piece of DNA from one location to another
Which chromosomal aberrations can be large-scale changes
- Deletions
- Duplications
- Insertions
- Inversions
A transition mutation is considered a type of point mutation
What is it
Changes a purine for a purine OR a pyrimidine for a pyrimidine
point mutations can either be
- Silent (missense or nonsense) due to base substitution
- Frameshift due to alteration of the reading frame with an insertion or deletion mutation
What is an Open Reading Frame (ORFs)
A section of DNA or RNA that codes for a protein
Since 3 of the 64 codons are stop codons, on average we expect to encounter a stop codon every 20 amino acids in a random sequence
How does this help us to work out where an open reading frame is
A gene which has very few stop codons is likely to be the reading frame for a protein
As you would have expected to have had a stop codon
Say you had a sequence with two AAs randomly in the middle
How could you work out if it was an insertion or a deletion
You could translate both sequences and look for the longest open reading frame
Or to sequence more individuals from the same or closely related species
Depending on the mutation, point mutations can have what affect on the protein
- No effect (same-sense, mis-sense)
- Change of function (mis-sense, small deletions)
- Loss of function (mis-sense, nonsense and frameshift)
Why my some mutations be more disruptive than others
Amino acid substitutions affecting structural features or the catalytic site are likely to have major effects on protein activity
Bacteria and yeast are examples of haploids, whereas humans are an example of diploids
How does the show in the effect of the mutation
Mutations of haploids always show in the phenotype
Mutations of diploids can prevent gene product synthesis OR there is no effect and hence no mutant phenotype OR an intermediate where there is a wild type and mutant gene (1:2:1 ratio)
What is the DNA replication error rate
10⁻⁹
Knowing what the DNA replication error rate is, how likely is there a mutation in an E.coli
E.coli only have a genome of ~10⁶
This means only 1/1000 cells has a mutation in any base pair
Hence replication is extremely accurate due to the size of their genome
Define Mutagen
A chemical or physical agent that cause damage (a lesion) to the genetic material)
Define DNA damage
Chemical alteration of the DNA
What is DNA repair
The removal/reversal of the damage to DNA
What is the difference between spontaneous and induced DNA damage
Spontaneous: Errors during DNA replication
Induced: Mutagen, lesions and DNA damage
What is mismatch
When the wrong base has been added by tRNA to replicating DNA
(e.g. G instead of A)
Then is the following subsequent round of replicating, it becomes a substitution mutation
What is a Lesion
A Lesion is an alteration to the chemical structure of one of the components of DNA
What is the difference between a nick and a chromosome break
Nick: break in the one phosphodiester backbone (relatively easy to repair)
Chromosome break: Break in both phosphodiester backbones
List the categories of DNA damage
- Adduct (single or double stranded)
- Nick or Chromosome break
- Mismatch
- Cross-link
What are the two ways the cell can repair DNA damage
- Direct repair
- DNA excision repair (damaged piece of DNA is removed, then reinstated)
Define ‘Direct Repair’ of DNA
A reversal of the chemical reaction causing the lesion
What is the name of the process which causing mispairing of G with T
How it is reversed
O⁶-Methylguanine
Using the enzyme methyltransferase
Define ‘DNA excision repair’
Removal and resynthesis of a damaged DNA section
Thymine dimer is an example of DNA excision
What does it involve
A bond between two adjcent thymines on the same DNA strand
Makes it difficult for polymerase to replicate the DNA strand
