Mutation: origin, pattern and implications Flashcards
Are somatic mutations heritable?
no
What are the molecular mechanisms of mutational hotspots?
- transitions at CpG dinucleotides
- slipped mispairing at DNA replication
What happens when there is slipped mispairing at DNA replication.
- changes in repeat number in a microsatellite repeat
- offspring has an allele of a different size than either parent
- mutator phenotype seen at multiple loci
Is disease incidence greater or lesser with paternal age?
increased
Why is there a high male mutation rate?
- large difference between sexes in the large number of germ cell divisions
- male has about 310 divisions (by the time the male has reached his 20s)
- female has 24-31 divisions
- errors in DNA replication/repair produce the great majority of mutations
Why does mutation of germ cell rate increase with age in males?
-more rounds of DNA replication so larger chance of error and therefore mutation
What does accurate DNA sequencing allow us to do?
- compare the mutations in both parents with offspring
- therefore get an estimate of new mutations produced in each generation
What does each year of paternal age result in?
an average of 2 extra mutations in offspring
Why is there an acceleration in mutation rate with paternal age?
contributions include:
- reduced fidelity of DNA repair and replication mechanisms
- cell death in old age might be compensated by increased number of cell divisions
- accumulation of mutagens
What are the exceptions to the paternal age affect?
- neurofibromatosis I
- Duchenne muscular dystrophy
Why are deletions common in large genes?
they have space to take them (deletions in smaller genes would be lethal)
Is the rate of deletions higher in males or females?
females
Are small chromosome deletions age dependent?
no because they occur through a different mechanism
When does Huntingdon’s disease occur?
when there are 37-84 repeats of CAG
Why is having a low mutation rate bad?
leads to non-adaptive species
