Chromosomes: normal and aberrant structure and karyotypes

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Chromosomes normal and aberrant structure and
karyotypes

• Chromosomes are comprised of a single,
  uninterrupted DNA molecule complexed with
  proteins (histones and others).
• Landmarks of human chromosome structure include
  telomeres and the centromere demarcating the two
  arms (p and q).
• A karyotype is a visual display of the
  chromosomes of an individual.
• A human karyotype is generally prepared from
  cultured white blood cells treated with a mitogen
  and then colchicine to arrest cells in mitotic
  metaphase (chromosomes highly condensed and
  visible). Cells are then swollen hypotonically
  and chromosomes released onto a slide and then
  stained to reveal species-specific banding
  patterns of individual chromosomes. FISH can be
  performed for mapping.

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Klug and Cummings, 6th Ed., 2000
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Chromosome numerical variations

• Polyploidy extra complete sets of chromosomes,
  e.g., 3n (triploidy). This is found in some
  spontaneously aborted human fetuses.
• Aneuploidywrong number of chromosomes, e.g.,
• 2n 1 trisomy, the presence of an extra copy
  of one specific chromosome
• 2n - 1 monosomy, the absence of one copy of a
  specific chromosome
• Origins of aneuploidy most frequently lie in
  meiotic nondisjunction

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Common human aneuploidies

• There are no viable human monosomies except that
  of the X chromosome XO, Turner syndrome.
• Other sex-chromosome aneuploidies associated with
  viability are XXY (Klinefelter syndrome) and XYY.
• Most human autosomal trisomies are embryonic
  lethals, but Ts 13, 18 and 21 survive in many
  cases.
• The most viable human trisomy is Ts21, Down
  syndrome. Incidence of nondisjunction-related
  Ts21 increases with increasing maternal age.
• Abnormalities and lethality associated with
  monosomy and trisomy suggest tight dosage
  control, with no dosage compensation.

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Chromosomal structural aberrations

• The most frequent structural aberrations include
  deletions, duplications, inversions, and
  translocations.
• These abnormalities of structure can give rise to
  abnormalities in meiotic segregation of
  chromosomes as well as further structural
  abnormalities after crossing over.
• Translocations can be reciprocal or
  non-reciprocal, or Robertsonian centric fusions.

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Chromosome structure and aberrations Summary

• Important landmarks of chromosome structure
  includes telomeres, a centromere and the arms.
• Construction of karyotypes enables not only
  cytogenetic analysis of defects but also gene
  mapping (e.g., by FISH).
• Aberrations of chromosome number include
  polyploidy and aneuploidy, but aneuploidy is much
  more common in humans.
• Aberrations of structure include inversions,
  deletions, duplications and translocations, both
  reciprocal and non-reciprocal. These can be
  useful reagents for gene mapping.