Mutations and gene expression

• Mutations are changes in the base sequence of DNA and this can be any change and are caused by errors during DNA replication
• substitution


  one or more bases are swapped for another
• deletion


  one or more bases are removed
• addition


  one or more bases are added
• duplication


  one or more bases are repeated
• inversion


  a sequence of bases is reversed
• translocation


  a sequence of bases is moved from one location in the genome to another. this could be a movement Dothan the same chromosomes or movement in different chromosome
• the sequence of DNA bases in a gene determines the sequence of amino acids in a particular polypeptide. if a mutation occurs in a gene the sequence of amino acids in the polypeptide that it codes for could be changed
• polypeptides make up proteins so a change in the sequence of amino acids can change the tertiary structure of the protein which could mean that it doesn’t work properly and so will lead to a change in active site and therefore not be able to catalyse the reaction anymore
• some mutations can cause genetic disorders and these can be inherited disorders that are caused by abnormal genes or chromosomes
• if a gamete containing a mutation for a genetic disorder or a type of cancer is fertilised the mutation will be present in the new fetus formed and these are called hereditary mutations because they have been passed on
• Not all mutations affect the order of amino acids
• the degenerate nature of the genetic code means that some amino acids are coded for by more than one DNA triplet and so this means that not all types of mutation will always result in a change to the amino acid sequence of the polypeptide
• example of mutations that may not affect the sequence of amino acids are:

  • some substitutions
  • sometimes inversion
• mutations that will result in the change of amino acid sequence are:

  • additions
  • duplications
  • deletions

  and this is because those mutations all change the number of bases in the DNA code and so causes a frameshift in the base triplets that follow and resulting in the triplet code being read in a different way
• mutagenic agents increase the rate of mutations and examples of these agents are:

  • ultraviolet radiation
  • ionisation radiation
  • some chemicals
  • some viruses
• mutagenic agents increase rate of mutations by:

  • acting as a base - base analogs can be substitute for a base during DNA replication, changing the base sequence in the new DNA
  • altering bases - some chemicals can delete or alter bases
  • changing the structure of DNA - some types of radiation can change the structure of DNA which causes problems during DNA replication
• mutations in genes can cause uncontrolled cell growth
• acquired mutations - mutations that occur in individual cells after fertilisation
• if mutations occur in the gene which controls the rate of cell division it can lead to uncontrollable cell growth and is a cell divides uncontrollably the result is a tumour.
• there are two types of gene that control cell division:

  • tumour suppressor genes
  • proto-oncogenes
• a mutations in the tumour suppressor gene can cause cancer by

  1. when functioning normally tumour suppressor genes slow cell division by producing proteins that stop cells dividing or cause them to self-destruct
  2. is a mutation occurs in a tumour suppressor gene the protein isn’t produced so the cells divide uncontrollably and the rate of division increases and results in a tumour
• a mutation in the proto-oncogenes can lead to cancer by:

  1. when functioning normally proto-oncogenes stimulate cell division by producing proteins that make cells divide
  2. if a mutation occurs in a proto-oncogenes the gene can become over activated and this stimulates the cell to divide uncontrollably and the rate of division increases and results in a tumour
• malignant tumours - are cancerous and usually grow rapidly and invade and destroy the surrounding tissues. cells can break off the tumours and spread to other parts of the body in the bloodstream or the lymphatic system
• benign tumours - are not cancerous and grow slower than malignant tumours and are often covered in fibrous tissue that stops cells invading other tissues. benign tumours are often harmless but the can cause blockages and put pressure on organs and some benign tumours can become malignant tumours
• tumour cells can differ from normal cells in different ways for example:

  • have irregular shape
  • nucleus is larger and darker and may have multiple
  • dont produce all the proteins needed to function properly
  • different antigens on their surfaces
  • dont respond to growth regulating processes
  • undergo mitosis more frequently
• methylation - the addition of a methyl group onto something
• methylation of DNA is a important method of regulating gene expression and it can control whether or not a gene is transcribed and translated
• hypermethylation - when methylation has happened too much
• hypomethylation - when not enough methylation is happening
• When tumour suppressor genes are hypermethylated the genes are not transcribed so the proteins they produce to slow down cell division aren’t made and this means that cells are able to divide uncontrollably by mitosis and tumours can develop
• hypomtheylation of proto-oncogenes causes them to act an oncogenes which increase the production of the proteins that encourage cell division and this stimulates cells to divide uncontrollably which causes the formation of tumours
• increased exposure to oestrogen over an extended period of time is though to increase a woman’s risk of developing breast cancer.
• theory of how oestrogen can contribute to breast cancer:

  1. oestrogen can stimulate breast cells to divide and replicate by more cell divisions taking place it increases the chance of mutations occurring so increase chance of being cancerous
  2. this ability to stimulate division could also mean that if cells do become cancerous their rapid replication could be further assisted by oestrogen helping the tumours to form rapidly
  3. other research suggests that oestrogen is actually able to introduce mutations directly into DNA of certain breast cells which will also increase the chance of being cancerous
• genetic factors of cancer: some cancers are linked with specific inherited alleles. if you inherit that allele you're more likely to get that type of cancer
• environmental factors: exposure to radiation, lifestyle choices, increased alcohol consumption and a high fat diet
• examples of genetic factors for cancer: BRCA1 and BRCA2 mutations
• prevention of cancer

  • if a specific cancer-causing mutation is known then it is possible to screen for the mutation in the persons DNA
  • knowing about the increased risk means that preventative steps can be taken to reduce it
  • knowing about specific mutations also means that more sensitive tests can be developed which can lead to earlier and more accurate diagnosis
• treatment and cure for cancer

  • the treatment for cancer can be different for different mutations so knowing how specific mutations actually cause cancer can be very useful for developing drugs to effectively target them
  • some cancer-causing mutations require more aggressive treatment than other so understanding how the mutation that causes them works can help produce the best treatment plan
  • gene therapy may also be used to treat cancer caused by some mutations
• totipotent stem cells are able to mature into any type of body cell