Lecture 14 Flashcards
Mutation definition
a change in the nucleotide sequence in DNA
Mutagenesis definition
the process of mutation generation
e.g. DNA damage
Stages for a mutation to occur…
Mutation -> Defective/error prone DNA repair -> Mutation
Three groups of types of causes of mutation
- Endogenous
- Exogenous
- Spontaneous events
Summary of mutations
Recap - types of DNA damage
Spontaneous mutation - spontaneous deamination
Can see very quickly that gone from:
C to T (this is a permanent change)
G A
With deamination what is the change in amino acid?
Cytosine ->
5-methylcytosine ->
Cytosine -> uracil
If the cytosine is methylated: 5-methylcytosine -> thymine
Spontaneous mutation - Transposable elements (TEs)
- specific repetitive DNA sequences that move (transpose)
- ‘jumping genes’ or transposons
- ubiquitous (found in all life forms)
- discrete units that transpose randomly
- supernumerary (lots of copies - 45% of the human genome is transposable elements)
- can make up a very large percentage of a genome
- causing mutations (changes in nucleotide sequence)
- These specific DNA can move as discrete units within a chromosome or from one chromosome to another chromosome
- DNA is thought to have a specific position, therefore transposable elements can move
Spontaneous mutations - Transposable elements - the effect of these…
Remember - this is one a transposable element can move randomly to somewhere else e.g. outside the gene or within a gene
- no effect
- inactivate
- re-activiate
- alter gene expression
In picture:
- Protein product is not functional as it is in the middle of a gene
- Transcription activated in other cell types as the transposable element here has jumped into the promoter region
- No effect as the transposable element has moved outside the cell
NOTE - IF THE TRANSPOSABLE ELEMENT JUMPS OUT OF THIS GENE AGAIN = IT COULD RE-ACTIVATE THE GENE
Is a mutation (good/bad, phenotypic effect…, why does it occur?)
A change in the nucleotide sequence in DNA
- may or may not cause a phenotypic change
- may be ‘good’, ‘bad’ or neutral
- is a source of genome variation
- is the driving force of evolution
- may cause disease
Mutations are important at which levels?
Nucleotide and gene level (e.g. deletion, insertion, substitution)
Chromosome level
What is Single Nucleotide Polymorphism?
A single-nucleotide polymorphism (SNP, pronounced snip) is a DNA sequence variation occurring when a single nucleotide adenine (A), thymine (T), cytosine (C), or guanine (G]) in the genome (or other shared sequence) differs between members of a species or paired chromosomes in an individual.
What are the three types of SNP?
- no known effect – anonymous SNP
- outside a gene – non-coding SNP
- inside a gene – coding SNP
The two types of mutation which change a single nucleotide (single nucleotide changes)
Transition:
• change to same type of base purine to purine
(A<–>G ) pyrimidine to pyrimidine (T<–>C)
Transversion:
• change to different type of base purine to pyrimidine or vice versa (A/G<–>C/T)
What can the effects be of a single nucleotide change?
- change gene product (polypeptide or RNA)
- change the amount of gene product
- change the polypeptide length
- do not have an effect
What is the genetic change in sickle cell aneamia? (learn)
Single nucleotide changes mutation in codon 7 of HBB
• transversion A>T of 2nd base
• amino acid change Glu>Val
• Sickle Cell phenotype
• missense mutation
What is a missence mutation?
Non-synonymous mutation (means that it causes a change in the amino acid)
The mutation causes a change in the amino acids
The mutations that can occur in codon 7 of HBB - and the affect of these
Single nucleotide changes mutation in codon 7 of HBB
• GAG>GTG, Glu>Val, missense, Hb Sickle Cell
• GAG>GCG, Glu>Ala, missense, Hb G Makassar
• GAG>AAG, Glu>Lys, missense, Hb C
• GAG>GAA, Glu>Glu, neutral/silent, no phenotypic change
What does neutral/silent/synomyous mean?
Amino acid sequence is not modified
Checkpoint…
Single nucleotide changes
• change gene product (polypeptide or RNA)
-> change in amino acid: missense / non-synonymous
• change the amount of gene product
• change the polypeptide length
• do not have an effect
-> silent or neutral / synonymous
What type of mutation can cause a change in the polypeptide length?
Two scenerios:
- Frameshift (changes the reading frame)
- Mutation to the stopcodon
e. g. To make a stop codon or to change the stop codon into something else. Make a mutation that makes a stop codon, so polypeptide is shorter than it should be (nonsense mutation)
Single nucleotide changes
Mutation to the stop codon:
HBA1 (length of a-polypeptide = 141aa)
139 1 42
AAA UAC CGU UAA GCUGGAGCCUCGGUAGCC
Lys Tyr Arg STOP………untranslated……
Framshift resulting in the wrong position of the stop codon:
a-Wayne (length of mutant a-polypeptide = 146aa) 139 142 147
AA*U ACC GUU AAG CUG GAG CCU CGG UAG CC Asn Thr Val Lys Leu Glu Pro Arg STOP…
* is the deletion of A, this has changed the reading frame, so the stop codon is not recognised anymore = longer polypeptide (frameshift, could also result in a shorter polypeptide)
What is a frameshift mutation?
Mutation that causes a change in the reading frame
Frameshift mutation is a genetic mutation caused by indels of a number of nucleotides in a DNA sequence that is not divisible by three. Due to the triplet nature of gene expression by codons, the insertion or deletion can change the reading frame, resulting in a completely different translation from the original.
What does the following mean: Non-overlapping triplet code?
5’-THEBIGOLDCATATETHEFATRAT-3’
Frame 1 (0): THE BIG OLD CAT ATE THE FAT RAT
Frame 2 (+1): T HEB IGO LDC ATA TET HEF ATR AT
Frame 3 (-1): TH EBI GOL DCA TAT ETH EFA TRA T
