Chromosomal abnormalities

• Chromosomal abnormalities

  Deviations from the normal chromosome number or structure
• Cytogenetics

  The study of the structure and function of chromosomes
• Karyotype

  A preparation of chromosomes arranged in size order
• Making a Karyotype

  1. Draw 10-20 ml of blood

  2. Add phytohaemagglutinin to stimulate mitosis

  3. Incubate 2-3 d

  4. Treat with colcemid for 1-2 h to stop mitosis in metaphase

  5. Transfer cells to tube, pellet cells by centrifugation

  6. Add hypotonic solution to lyse cells

  7. Transfer to tube containing fixative

  8. Stain slide with Giemsa

  9. Drop cells onto microscope slide

  10. Examine with microscope, photograph metaphases

  11. Arrange chromosomes into a karyotype
• Chromosomes

  • Length
  • Banding pattern
  • Placement of centromere
• Karyotyping

  The three ways to identify a chromosome
• Normal male karyotype (not Giemsa stained)
• Normal female karyotype (Giemsa stained)
• Karyotyping used for

  • A. to detect changes in chromosome number
  • B. to detect changes in chromosome structure
• Polyploidy


  Extra whole sets of chromosomes
• Polyploidy is rare in animals, common in plants (e.g. bananas)
• • Wild banana; 2n =22
  • Cultivated banana (seedless) 3n =33
• Aneuploidy

  Some additional or missing chromosomes
• Monosomy


  One chromosome missing
• Trisomy


  One extra chromosome
• This karyotype would be written as: 47,XX,+18
• Non-disjunction

  The cause of aneuploidy
• Non-disjunction

  1. Non-disjunction of sister chromatids in Meiosis II

  2. Non-disjunction of homologous chromosomes in Meiosis I
• Aneuploidy occurs in 50% of human conceptions
• Most aneuploidies lead to embryonic death or spontaneous abortion
• The only autosomal aneuploidy that permits survival into adulthood is Down's Syndrome
• Aneuploidies of the sex chromosomes are more common e.g. XO and XXY or XXXY
• Characteristics of Down's Syndrome

  • Characteristic facial features
  • Short stature
  • Sterile
  • Intellectual disability
  • Heart defects; susceptibility to leukaemia and Alzheimer's disease
• Incidence of Down's syndrome increases with maternal age
• Screening for chromosomal abnormalities

  • Amniocentesis and karyotyping
  • Blood tests to detect specific proteins associated with a Down's foetus
  • Ultrasound scans - to measure the size of the nuchal pad at the nape of the foetal neck associated with Down's syndrome
• Turner's syndrome (45, XO)

  The only viable human monosomy; 1 in 2500 live female births
• Characteristics of Turner's Syndrome

  • Phenotypically female
  • Sterile due to lack of maturation of sex organs
  • Oestrogen replacement therapy leads to development of secondary sex characteristics
• Klinefelter's syndrome (47, XXY)


  One of the most common genetic abnormalities (1:500-1000 live male births)
• Characteristics of Klinefelter's Syndrome (47, XXY)

  • Essentially male, but with some female characteristics
  • Sterile
  • May have intellectual disability
  • Tall stature
  • Treated with hormone replacement therapy (testosterone)
• • X0 (Turner's syndrome) - essentially female
  • XXY (Klinefelter's syndrome) -essentially male
  • (Even XXXY or XXXXY are male)
• It is the presence or absence of the Y chromosome that determines gender
• Chromosomal mutations

  Different types of change in chromosome structure
• Each G-band can be given an 'address' – allows specific chromosomal mutations to be accurately described
• Changes in chromosome structure

  • Deletions
  • Translocations
• Cri-du-Chat Syndrome

  • '5p Minus syndrome', 'Le Jeune's syndrome' ~1 in 50,000 live births
  • Deletion of part of the short arm of chromosome 5
• Characteristics of Cri-du-chat Syndrome

  • Babies have cat-like cry
  • Defects in glottis and larynx
  • Wide face with saddle nose
  • Physical and intellectual disability
  • Range of severity, depending on the extent of the deletion
• Prader-Willi Syndrome

  • Deletion in long arm of chr 15 (15q1.12)
  • ~1:15,000 live births
• Characteristics of Prader-Willi's Syndrome

  • Poor suckling reflex in infants
  • Uncontrollable eating in later life
  • Obesity
  • Diabetes
  • Poor sexual development in males
• Prader-Willi's Syndrome only occurs when the affected chromosome is inherited from the father – due to genomic imprinting
• Angelman's Syndrome


  Arises if the same segment is missing from the maternally derived chromosome 15 (because the imprinted genes on the other chromosome are different in each case)