Gene Mutations Flashcards
What is a gene mutation?
an alteration in the nucleic acid sequence of the genome of an organism
How do gene mutations arise?
- Errors during replication
- Mutagens
What errors occur during replication?
- Point mutations
- Replication slippage
What does Ultraviolet cause?
- causes dimerization of adjacent pyrimidine bases (esp thymines)= deletion mutation
What is dimerization?
the process of joining two identical or similar molecular entities by bonds
What does ionising radiation cause?
Electromagnetic waves and particles= direct and indirect damage
What is an example of indirect damage caused by ionising radiation?
Free radicals which attach to DNA strand and break pieces off
What chemicals are classed as mutagens?
asbestos
cyanide
alcohol
sawdust
disinfectant
What are the general approaches against mutation?
1- Prevent
2- Repair
3- Give up (apoptose the whole cell)
What does prevent involve?
- Melanin (protect DNA in skin)
- Peroxisomes (an organelle that makes antioxidant enzymes)
- Good life choices
What does repair involve for Nicks? (mutagens)
phosphodiester bond breaks which DNA ligase repairs
What does repair involve for single stranded damage to bases? (mutagens)
base excision repair for small bits of damage and nucleotide excision repair for big bits of damage
What does Polymerase III do to repair mutations caused during DNA replication?
Proofreading activities
What other form of repair is there if mutation is caused by DNA replication?
Mismatch repair, 4 proteins detect lack of hydrogen bonds between mismatched base pairs, and then repair
What 4 proteins are involved in mismatch repair?
MSH2
MSH6
MLH1
PMS2
Why is giving up sometimes the best option?
There may be too many mutations for cells to repair
Apoptosis (programmed Cell death) is initiated
Examples of giving up
- Sunburn with blistering
- Radiotherapy treatment
- Radiation sickness
How does the location of mutation affect outcome?
Non-coding= no affect
Coding= potential for effect
What is frameshift?
Shifts reading frame (rest of protein effected), caused by insertion or deletion of non multiples of 3
What is a silent mutation?
different base, but still codes for the same amino acid so no effect
What is a Missense mutation?
changes to a different amino acid, only affects one amino acid so small effect especially if similar shape/ charge
What is a nonsense mutation?
changes codon to a stop codon, big effect if at start of protein
How can a mutation cause cancer?
Mutation in gene that normally controls cell division
oncogenes or tumour supressor genses= potential to cause cancer
What are Germline cells?
cells in body that make sperm and eggs
What are somatic cells?
All other body cells
How can a mutation effect the phenotype of offspring?
If mutation occurs on a relevant protein and in a germline cell= potential to change phenotype of offspring
Could be harmless change or cause a genetic disease
Possibility for selective advantage
What is Cystic Fibrosis?
Autosomal recessive condition
Caused by one of many mutations in gene encoding the CFTR protein
What is CFTR?
cystic fibrosis transmembrane conductance regulator
What does CFTR do?
Is a membrane protein that transports chloride ions
What happens if CFTR is defective?
Cl ions cannot exit cells
Sodium (thus water) follow Cl out of mucus into cell
Less water in mucus
thick mucus= recurrent infections
What is Neurofibromatosis (NF)?
Autosomal dominant
Caused by a mutation in one of 2 genes
In what protein can mutations occur to cause NF
Neurofibrin protein= NF1
Merlin protein= NF2
What do NF1 & NF2 proteins control?
Control cell cycles as “tumour suppressor genes”
What is the most common tumour for NF1?
Neurofibromas
What is the most common tumour for NF2?
Schwannomas
What is Phenylketonuria?
Autosomal recessive
Caused by mutation in the gene coding for the protein phenylalanine hydroxylase
What is phenylalanine hydroxylase responsible for?
This enzyme is responsible for metabolising the amino acid phenylalanine
Why is phenylketonuria variable?
Very dependant on early dietary modification
If phenylalanine free diet= near normal phenotype
If phenylalanine rich diet= build up in brain
What is Huntington’s Disease?
Autosomal dominant
Affects men & women equally
Caused by increased CAG trinucleotide repeats in the gene that codes for huntingtin protein
What age does huntington’s disease normally present?
30 to 50
What is the huntingtin protein normally involved in?
Usually involved in transport along neronal axons
Is Huntington’s disease variable and what are some symptoms?
-YES
progressive inability to control body movements
Change in mood/ personality
Symptoms are more severe and onset earlier with more CAG repeats
More CAG repeats occur with each generation
Where is the huntingtin gene located?
short arm of chromosome number 4
What are trinucleotide repeats?
A sequence of three bases repeated numerous times
Why do trinucleotide repeats occur?
Due to slippage off DNA polymerase
How will increased trinucleotide repeats in the huntingtin gene affect the huntingtin protein and cause symptoms?
An abnormally long version of the huntingtin protein is made, which doesn’t function properly and instead accumulates in neurons, disrupting the normal functions of these cells
Why does Huntington’s show an increased severity and earlier onset every time it is passed down to subsequent generations?
The longer a trinucleotide CAG repeat is, the more unstable during replication. This means even more slippage of DNA polymerase will occur with each replication, elongating the gene further each time
