mutations

• mutation is a permanent change in the DNA of a cell
• chromosomal mutation 


  a change in gene position or number
• point mutation 


  a change in nucleotide sequence
• mutations are important becuase

  source of variation, cause of disease
• mutations are rare, randomly occur and are usually detrimental
• mutations in somatic tissue are not passed on to offspring, but are passed on to all cells descending from the original mutant
• mutations in germ-line cells are passed on to offspring, cause of inherited genetic disease, material which causes natural selection (and produces evolutionary change)
• null mutation is where

  no protein is made at all
• base pair substitution can cause

  • no effect on the amino acid sequence
  • missense where amino acid is changed
  • nonsense where stop codon is coded for instead of amino acid
• base pair substitution that causes severe consequences

  sickle cell anaemia where single nucleotide in haemoglobin is changed, glutamic acid is changed to valine
• glutamic acid is large, charged and has a hydrophilic side chain
• valine is small, nonpolar, hydrophobic side chain
• base pair insertion/deletion can cause

  • frameshift causing extensive missense
  • frameshift causing immediate nonsense
  • insertion or deletion of 3 nucleotides causing either no frameshift, extra or missing amino acid
• causes of a mutation

  • spontaneous
  • induced
• spontaneous mutations are through DNA replication
• induced mutations can be

  chemical or physical
• DNA replication errors 


  normal amino cytosine pairs with guanine, imino form of cytosine pairs with adenine
• chemical mutagens

  • base analogues
  • modifying agents
  • intercalating agents
• physical mutagens

  • ionising radiation
  • UV radiation
• base analogues are 


  chemicals that resemble DNA bases but pair incorrectly when incorporated in DNA
• 5 bromouracil can be incorporated into DNA as if it were

  thymine
• 5 bromouracil tends to rearrange to form that resembles cytosine after bonding, which can then result in a point mutation occuring
• modifying chemical agents can remove the amino group from adenine or cytosine
• when deaminated C is replicated, A is inserted
• deamination occurs spontaneously at low rates
• uracil is not usually found in DNA, uracil DNA glycosylase role is to 


  remove U from DNA to prevent mutations
• modifying chemicals can add hydrocarbon groups to nucleotide bases
• adding hydrocarbons can alter the base pairing characteristics, when added to the O6 position
• intercalating agents are inserted between bases and distort the DNA helix

  • therefore interfere with replication
  • tend to cause frameshift mutations
  • e.g. ethidium bromide
• ionising radiation directly ionises DNA, ionises water to produce free radicals
• ionising radiation can damage bases and cause double strand breaks
• UV radiation mechanism causing mutation

  • absorbed by pyrimidine bases (C and T)
  • covalent bonds can form between adjacent T or C nucleotides (pyrimidine dimers)
  • blocks DNA synthesis leaving a gap opposite site of damage
• thymine dimers can be removed by

  nucleotide excision repair (NER)
• NER works by

  • recognises distortion in helix
  • nuclease enzyme cuts out damaged DNA
  • repair synthesis by DNA polymerase to fill the gap
  • DNA ligase seals remaining nick
• xeroderma pigmentosum is a hereditary disorder that individuals are deficient in 


  NER
• cancer is a disease caused by mutations