gene mutations and chromosomal aberrations

• point mutation: change in a single base
• substitution mutation: one or more nucleotides replaced by another nucleotide
• silent mutation

  • change in base sequence but no change in amino acid being coded for (degenerate code, multiple codons can code for the same amino acid)
  • no change on structure and function of polypeptide
• nonsense mutation

  • introduction of a stop codon in mRNA strand due to change in base sequence
  • translation is terminated prematurely, polypeptide is truncated, protein is likely to be non-functional
• conservative missense mutation

  • change in base sequence results in change in amino acid coded for
  • changed amino acid has similar chemical properties (similar R-group) to original, protein function unaffected
• non-conservative missense mutation

  • change in base sequence results in change in amino acid coded for
  • changed amino acid has different chemical properties (diff R-group), protein function will be affected
• Insertion and deletion mutation

  • one or more nucleotides added or removed
  • diff sequence of amino acids encoded
  • frameshift mutation can take place where incorrect triplets are read
• inversion mutation

  • segment of nucleotide sequence separates from allele and rejoins but is inverted
  • length of segment inverted is highly variable
• how does sickle cell anaemia occur

  • codon on DNA template changes from CTC to CAC
  • results in change in codon in mRNA from GAG to GUG
  • amino acid changed from glutamate to valine on B-globin chain
• R-group of glutamate is charged, hydrophilic
• R-group of valine is non-polar, hydrophobic
• effect of the mutation in sickle cell anaemia

  • R-group property changed from charged, hydrophilic to non-polar, hydrophobic (glutamate to valine)
  • at low oxygen, HbS polymerises into rigid rodlike fibres as hydrophobic regions of molecules can form hydrophobic interactions
• impacts of health due to sickle-cell anaemia

  • sickle red blood cells more fragile and actively destroyed in spleen, leads to shortage of red blood cells and poor oxygen transport → breathlessness, anaemia, heart failure
  • sickle red blood cells less flexible, can be lodged in small blood vessels and capillaries → deprive organs of oxygen and cause damage
• chromosomal aberrations: change in chromosomal structure and number
• deletion and duplication of chromosome segments

  • occurs during crossing over
  • non-sister chromatids of homologous chromosomes break and rejoin at incorrect places, one chromatid gives up more than it receives, one chromatid has less alleles (deletion) the other has multiple of the same gene (duplication)
• inversion: reverses a segment within a chromosome
• translocation: move a segment from one chromosome to another non-homologous chromosome
• aneuploidy

  • chromosomes present in extra or fewer copies (2n+1 or 2n-1)
  • result of non-disjunction where chromosomes of sister chromatids fail to separate properly (via failure of centromere division)
• Down’s syndrome

  • result of aneuploidy
  • non-disjunction during meiosis I
  • extra chromosome 21 (2n+1)
• Polyploidy

  • 3 or more times the haploid number of chromosomes
  • 3n, 4n
  • non-disjunction of entire chromosome sets