Mutations

Cards (14)

  • Mutation = alteration in the nucleic acid sequence of the genome
  • Detecting mutations:
    • maize - mutation in the C allele leads to a single white seed, allowing mutation rate to be calculated
    • frequency of spontaneous neurofibromatosis (dominant mutation) and haemophilia (sex-linked loci)
    • sequencing genes over subsequent generations
  • Indirect methods of detecting mutations - problems with incomplete penetrance, variance in loci mutation rate, and effect on the environment (e.g. thalidomide and phocomelia)
  • Somatic mutations - because cells constantly replace themselves, associated with cancers (proto-oncogenes) (the higher the age, more likely risk of cancer because the body accumulates mutations over time)
    Can also be increased by the environment, e.g. smoking
  • Retinoblastoma - can affect in one eye due to a spontaneous mutation in somatic cells, but also can affect both eyes as they inherit a mutation-carrying allele from a parent then get a second spontaneous mutation
  • DNA repair enzymes - correct mutation errors, resulting in a low mutation rate in the human genome
    Genetic failure in these enzymes is associated with cancer (Bloom syndrome)
    Werner syndrome - associated with detrimental ageing due to faulty enzyme
  • Transposable elements - loci which increase the mutation rate at other loci, introducing the idea that the genome changed and was intrinsically (naturally) unstable
  • Mutagens = agents that increase the mutation rate
  • Electromagnetic radiation - X-rays are mutagens, a tiny amount has a large effect
    WW2 atomic bomb - initial survivors suffered from radiation sickness and fears of health of future generations
  • Ultraviolet as a mutagen - leads to formation of thymine dimers which inhibit DNA replication
    Can be repaired by excision enzymes, but mutations in this mechanism leads to xeroderma pigmentosum (very high sensitivity to sunlight)
  • Chemical mutagens (e.g. mustard gas) can cause radiomimetic burns and can be checked for using the Ames test
    Aflatoxin - mould on cheese and wheat and has a mutagenic effect
    Carcinogens, e.g. in coffee because of caffeic acid
  • Age as a mutagen - due to a build up in germ line mutations
    Paternal age associated with achondroplasia, autism and schizophrenia
  • Sequencing in Iceland - shows age as a mutagen and over 3 generations to calculate mutation rate
  • Telomeres - at the ends of chromosomes and lost every time it divides
    HeLa cells have an overactive telomerase enzyme which delays the ageing of cells