Mutation Flashcards
Background of mutations
Genes change by mutation. The can occur in both somatic and germ line cells. Mutations were first observed by Hugo de Vries who found new flower colours arose in Oenothera lamarckiana. Historically it was far harder to detect mutations in humans. Today it is relatively simple to sequence multiple generations in a family to calculate the mutation rates.
Various classes of mutation such as morphological. For example, loss and gain (Bithorax) of function mutations in Drosophila.
Detecting mutations
Conditional mutations in bacteria grown on medium with an antibiotic or lacking an amino acid.
Maize - triploid endosperm every cob a family of seeds; recessive “white” allele, c. Cross cc (female)
x CC (male) -> Ccc (coloured). Any mutation in the C allele will lead to a single white seed. Allows
mutation rate to be calculated which varies massively across the maize genome.
How to detect mutations in humans
The frequency of spontaneous cases of neurofibromatosis (caused by a dominant mutation) can be used to calculate mutation rate and to a lesser extent for sex-linked loci (e.g. haemophilia).
Problems with mutation detection
There are problems with this ‘indirect’ method including incomplete penetrance, variance in loci mutation rate and the confounding effect of the
environment (such as polydactyly).
More effective method is to directly sequence genes or genomes over subsequent generations.
Somatic mutations
Most mutations are somatic and occur during development (eg cat eye colour; many cancers). Cells in our body replace themselves and as such cancers are common in organs with a high turnover.
Our body cells accumulate mutations over time and consequently many cancers are associated with age. Somatic mutation rate can be increased by the environment such as smoking. Proteus
syndrome in humans is associated with overgrowth of bone, famous case being Joseph Merrick.
Somatic and germline mutations
Many cancers can be caused by either or both somatic and germline mutations. Retinoblastoma
(type of eye cancer) can affect one eye because a spontaneous mutation occurs in the somatic cells.
Some cases of retinoblastoma effect both eyes as they inherit a mutation carrying allele from a
parent and then get second spontaneous mutation.
Mutation rates in humans
Different groups of living organisms vary in mutation rate. The mutation rate of our genome is incredibly low because we have DNA repair enzymes which correct these errors. Many different mechanisms by which they proof read and correct our DNA.
Genetic failure in our repair enzymes is often associated with cancers. Bloom syndrome have a faulty repair enzyme and have high incidence of cancers. Werner syndrome which is associated with detrimental ageing.
Barbra McClintock
Found massive differences in the mutation rate of different loci in maize.
She found loci which increased the mutation rate at other loci. Today we call these loci transposable element and they are found in many other species such as Drosophila. This introduced the idea that the genome changed and was intrinsically unstable.
