topic 8

• Gene mutations are a change in the DNA base sequence of a gene
• Gene mutations mainly occur during DNA replication within interphase of the cell cycle
• Gene mutations occur randomly and spontaneously, but exposure to mutagenic agents increases the frequency
• Gene mutation


  Can result in a different amino acid being coded for, leading to a different tertiary structure and function of the protein
• Types of gene mutations

  • Addition
  • Deletion
  • Substitution
  • Inversion
  • Duplication
  • Translocation
• Addition mutation


  1. One extra nucleotide/base is added to the sequence

  2. Shifts all subsequent bases along one position

  3. Likely to code for a completely different tertiary structure and function
• Deletion mutation


  1. One nucleotide/base is deleted from the sequence

  2. Causes a frameshift with all subsequent codons changed

  3. Results in one fewer codon
• Substitution mutation


  1. One base is swapped for another

  2. Can result in a different amino acid being coded for

  3. May have no impact if in introns or result in the same amino acid
• Inversion mutation


  1. A section of bases detaches and rejoins in the opposite orientation

  2. Likely to code for different amino acids and a very different primary structure
• Duplication mutation


  1. One or more bases are duplicated in the sequence

  2. Causes a frameshift like addition and deletion
• Translocation mutation


  1. A section of bases detaches from one chromosome and attaches to a different chromosome

  2. Substantial alteration that can significantly impact gene expression and phenotype
• Stem cells


  Undifferentiated cells that can continually divide and become specialized
• Types of stem cells

  • Totipotent
  • Pluripotent
  • Multipotent
  • Unipotent
• Totipotent stem cells


  Can divide and produce any type of body cell
• Pluripotent stem cells


  Can divide into almost every cell type except placenta cells
• Multipotent stem cells


  Can divide to form a limited number of different cell types
• Unipotent stem cells


  Can only become one type of cell
• Induced pluripotent stem cells are produced from adult body cells using protein transcription factors
• Transcription factors


  Proteins that move from the cytoplasm into the nucleus and bind to DNA to stimulate or inhibit transcription of target genes
• Transcription factors bind to DNA


  Transcription of the gene can then occur
• Transcription factors do not bind to DNA

  The gene remains inactive and transcription will not occur
• Epigenetics


  Heritable changes in gene function without changes to the DNA sequence itself
• Increased DNA methylation


  1. Methyl groups bind to DNA

  2. Prevents transcription factors from binding

  3. Leads to tighter DNA/histone coiling and transcription inhibition
• Decreased histone acetylation


  1. Reduces negative charge on histones

  2. Allows tighter DNA/histone coiling

  3. Prevents transcription factor binding and inhibits transcription
• Euchromatin


  Less tightly coiled DNA that can be transcribed
• Heterochromatin


  Tightly coiled DNA that cannot be transcribed
• RNA interference (RNAi)


  1. Small interfering RNA (siRNA) binds to and destroys mRNA

  2. Prevents translation of the mRNA and production of the protein
• Cancer can result from mutations in genes that regulate mitosis
• Malignant tumour


  Grows quickly, cancerous, not encapsulated, can metastasize and spread to other tissues
• Benign tumors


  Not classed as cancerous, grow slower, have a capsule that prevents spread
• Malignant tumors


  Classed as cancerous, grow quicker, do not have a capsule, can metastasize and spread to other tissues
• Malignant tumors


  Cell nucleus becomes very large and returns to unspecialized state, do not produce adhesive layer or capsule, can metastasize and spread to other tissues
• Malignant tumors


  Can grow projections to reach blood supply, receive oxygen and glucose for rapid growth
• Removal of malignant tumors often requires supplementary treatment like radiotherapy and chemotherapy, and recurrence is more likely than with benign tumors
• Tumor development


  Can be due to gene mutation in tumor suppressor gene or oncogene, or linked to epigenetic changes like abnormal methylation or increased estrogen
• Oncogenes


  Mutated version of proto-oncogenes, code for proteins involved in initiating cell division
• Tumor suppressor genes


  Code for proteins involved in controlling the cell cycle and causing cell death
• Tumor suppressor gene mutation


  Protein not produced, cell division not slowed down
• Oncogene hypomethylation


  Gene permanently switched on, lots of protein produced to initiate constant cell division
• Tumor suppressor gene hypermethylation

  Gene switched off, protein not produced to slow down cell division