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