Chromo Mutations

• Types of mutations


  • Deletion - loss
  • Duplication - gain
  • Translocation
  • Inversion - relocation
• Chromosome


  • DNA highly packed into them
  • Chromos dense at M phase cell cycle - can be stained to study using light microscopy
• Karyotype


  • High resolution karyogram
  • Visualise chromo set - mitotic metaphase = chromosomes visible under microscope
  • More details seen by 'banding'
  • Computers aid
• Chromosome staining (G banding)


  1. Cells stimulated to divide with phytohemagglutinin (PHA)

  2. Arrested in metaphase with colcemid

  3. Chromo treated with tryspin

  4. Stained with Giemsa

  5. Sorted into auto mated procedure suing software
• G banding


  • Dark bands = AT rick & gene poor
  • Light bands = GC rich & gene rick
• G band genome mapping uses software
• FISH karyotyping

  • Standard FISH - single type of purified DNA fragment labellinga nd denaturation = homogenous DNA probe
  • Chromosome paining = complex mix of many diff DNA types from 1 chromo = heterogenous DNA probe
  • Chromo on slide - denature in situ allow to anneal expose to UV and visualise fluro (painting) or single probe bound (standard)
• Chromosome abberations in FISH are seen as different color probes - multiple regions
• Chromosome painting in FISH

  • Chromo-specific probes allow rapid identification of chromo
  • Used on uncultured cells from amniotic fluid in cancer cell analysis
• Comparative genomic hybridisation (CGH)

  • Deleting insertions & deletions
  • Chromosomal regions compated between proband DNA & referece DNA by hybridisation
• Array CGH


  Patient and reference or control - mix and hybridise - computer - gains of losses
• Chromosome abberations (chromosome microdeletions)

  • Cause dysregulation or loss of mutiple genes & combinesd gene dosage effects
  • Wrong protein amounts = diseases
  • Detected by CGH
• Chromosome mutation nomenclature


  • Pericentric = centromere
  • Paracentric = 1 arm affected
  • Balanced = no gains or losses of DNA
  • Unbalanced = gains or losses of DNA
• Chromosome numbers

  • Euploidy = wrong no of set of chromos
  • Monoploid = n 23, X
  • Diploid = 2n 46, XX
  • Triploid = 3n 69, XXX
  • Aneuploidity = wrong no of chromosome
  • Monosomic = 2n-1 45,XX-7
  • Trisomic = 2n+1 47,XX+21
• Non-disjunction


  • Results in gametes with extra chromo & missing chromo
  • Occurs in meiosis 1 0r 2
• Trisomy 21 is Down's syndrome
• Trisomy 18 is Edwards syndrome - prenatal growth deficiency, abnormalities, malformations
• Trisomy 13 is Patau syndrome - malformations
• Structural aberrations

  • Translocations
  • Deletions
  • Inversions
  • Insertions
  • Duplications
  • Isochromosomes
  • Ring chromosomes
• Structural aberrations are caused by double-stranded DNA breaks
• We have learnt that chromosomes can be studied with various staining procedures including G-banding, FISH, and CGH
• Karyotypes are named after chromosome numbers, sex chromosomes, and alterations, if any. Locations are named using chromosome number, arm and band
• Altered chromosome numbers (numerical aberrations) and altered chromosome structures (structural aberrations) may lead to disorders