Sesh 13 and 15: Mutations Flashcards
Define a mutation.
A heritable alteration in a gene or chromosome AND the process that produces the alteration.
What are transposable elements?
- Specific DNA sequences that have no fixed position
- Move as discrete units to random sites
- If they transpose into a gene, they inactivate it, so are an endogenous mutation source
What do all macromutations involve?
Double-strand breaks.
What are transitions and transversions?
- Transitions=mutation to same type of base e.g. Purine to purine
- Transversions=mutations to different type of base
What is nonsense-mediated decay of mRNA?
Cell recognises and degrades mutant mRNA, so that it is not translated into a mutant protein.
What is a proto-oncogene?
A normal version of a gene that can be mutated to form an oncogene, that can cause cells to become cancerous under certain conditions.
Why are gain of function mutations likely to be dominant?
Mutant protein has a new function that can’t be negated by an existing protein or allele.
Why is a loss of function mutation likely to be recessive?
The individual’s other allele producing functional protein can compensate.
Why are errors in DNA transcription common?
RNA polymerase does not have proofreading capacity.
Why is an error in DNA transcription unlikely to have a long-term effect?
- RNAs are quickly degraded
- May undergo nonsense-mediated decay of mRNA so won’t be translated
- RNAs aren’t inherited
- Multiple RNA copies, so is unlikely for same mutation to re-occur
Mutations in mitochondrial DNA are more likely to have a greater effect on what type of organs/tissues?
Ones requiring lots of energy e.g. Heart, brain, skeletal muscle etc
In early development, where do primordial germ cells start from and migrate to?
Start from mesentery of gut and migrate to gonads.
At what stage are oocytes paused at at birth in females?
Prophase I.
When is meiosis of female gametes complete?
Fertilisation.
How many polar bodies does each female gamete give rise to?
3
What type of cell is ovulated?
A secondary oocyte.
Why is the mutation rate 5X higher in male gametes than female?
- Higher no of germline divisions in spermatogenesis vs oogenesis
- Spermatogonia are continually active in males
Why do IVF programmes over-estimate the in vivo aneuploidy rate?
Many mutations in sperm would affect their ability to fertilise the egg, so they would be naturally selected against in vivo, but may not have been in vitro.
75% of clinically recognised miscarriages result from what?
Chromosomal abnormalities.
Why do male and female gametocyte mutations increase with age?
- Male- spermatogonium are continually active…older spermatogonia have been exposed to mutagens for longer
- Female- unknown…perhaps due to longer in meiosis arrest
What can result if mutations occur after fertilisation?
- Mosaic individual
- Abortion
- Teratogenesis-abnormal development
- Cancer/increased cancer risk
What is pharmacogenomics?
The study of how an individual’s genes affect their response to drugs.
How is achondroplasia inherited?
Autosomal dominant manner.
