Numerical Chromosomal Aberrations in Human Diseases

Zuzana Storchova, Max‐Planck Institute of Biochemistry, Martinsried, Germany

Published online: January 2011

DOI: 10.1002/9780470015902.a0001451.pub2

Numerical aberrations (whole chromosomal aneuploidy) represent a significant proportion of chromosomal changes found in humans. These aberrations can occur as a consequence of chromosome segregation defects during cell division. Segregation errors arising during reductive cell division, or meiosis, are upon fertilisation and subsequent embryo development constitutively present in all cells, resulting in whole organismal aneuploidy. Missegregation in mitosis leads to a mosaic distribution of aneuploidy. Aneuploidy is associated with pathological states in most organisms. Numerical aberrations represent a significant cause of pregnancy loss as well as abnormalities found in live births. Moreover, numerical aberrations are frequently found in ageing tissues or in tumour cells. Although the association of aneuploidy and cancer is known for almost a century, the dispute is still ongoing whether this is a cause or a consequence of cell transformation. Recently, new evidence is emerging that numerical aberrations significantly alter the physiology of eukaryotic cells and might indeed directly contribute to tumorigenesis.

Key Concepts:

  • Numerical chromosomal aberrations result from errors in chromosome segregations.
  • Trisomy, monosomy and polyploidy are among the major causes of spontaneous human abortions.
  • Trisomies compatible with survival often result in multiple defects.
  • Numerical chromosomal aberrations significantly alter physiology of eukaryotic cells.
  • Numerical chromosomal aberrations are frequently found in cancer cells and can contribute to tumorigenesis.

Keywords: numerical aberrations; aneuploidy; polyploidy; trisomy; tetraploidy; cancer

Figure 1. Sources of segregation errors during cell division. A – Bipolar attachment of the sister chromatids to the opposite spindle poles yields equal segregation of genetic information. B – A defect in spindle or kinetochores disables correct attachment. C – Lack of sister chromatid cohesion is incompatible with proper chromosome segregation. D – Failure to sense defects during cell division and to arrest the cells until the defects are corrected also results in chromosome missegregation.
Figure 2. (a) Normal maternal meiosis; (b) a nondisjunction error at maternal meiosis I; (c) a nondisjunction error at maternal meiosis II.
Figure 3. Possible origin of trisomy mosaicism. The trisomy originated with two maternal (red) and one paternal (blue) chromosome. Loss of a chromosome in a trisomic conceptus may lead to either biparental inheritance or uniparental disomy (UPD) (as shown), whereby both chromosomes have originated from the mother. The fetus may show both trisomic and diploid cells or there may be selective elimination of the trisomic cells from the majority of fetal tissues.
Figure 4. A tetraploid cell that arises due to cytokinesis failure (or through other defects) can undergo multipolar mitosis leading to inviable or aneuploid progeny. The persistent presence of extra centrosomes causes continuing chromosome instability.
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Related Sub-Topics:

Chromosome Segregation | Developmental Disorders | Gametogenesis and Fertilisation | Chromosomal Disorders | Genomic Disorders
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Article Title: Numerical Chromosomal Aberrations in Human Diseases
 
How to Cite close
Storchova, Zuzana(Jan 2011) Numerical Chromosomal Aberrations in Human Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001451.pub2]