Origins of Human Aneuploidy


At birth, at least 1% of humans have a clinically significant chromosomal abnormality. However, this represents a small fraction of those originally conceived as by the time of birth, natural selection has eliminated the vast majority of abnormal embryos and foetuses.

There are three stages in development when aneuploidy may arise: during gamete formation, at fertilisation or during the early stages of embryo development. Gamete formation differs significantly between males and females, affecting the incidence of aneuploid gametes, which is fourfold higher in females than in males. Molecular cytogenetic techniques have revealed the extent of full and mosaic aneuploidy in embryos created by in vitro fertilisation (IVF), explaining the high level of arrested development affecting these embryos. Maternal age is the most significant factor affecting the incidence of aneuploidy, but genetic anomalies in the parents are also important.

Key Concepts

  • Chromosomally abnormal conceptions are very high in humans, but the effects are lethal in almost all cases.
  • Aneuploidy may arise at three developmental stages: during gamete formation, at fertilisation or during embryogenesis.
  • Gamete formation (oogenesis or spermatogenesis) differs considerably between the sexes as males produce sperm throughout adult life, whereas females are born with a finite set of oogonia.
  • These differences are reflected in the fourfold higher aneuploidy rate in females versus males.
  • Maternal age is the most significant factor affecting the incidence of aneuploidy, but genetic variation, particularly chromosomal rearrangement, in a parent is also an important factor.

Keywords: aneuploidy; trisomy; monosomy; oogenesis; spermatogenesis; embryogenesis; translocations; inversions; gonadal mosaics

Figure 1. Robertsonian translocation between chromosomes 13 and 21 leading to a derivative chromosome, der(13;21), with loss of the short arms from both chromosomes. The derivative chromosome is present in three generations, but the birth of infants with Down syndrome is seen only in the third generation. Reproduced from Human Cytogenetics, in Embryos, Genes and Birth Defects. eds Ferretti, Copp, Tickle and Moore, 2nd edn., Wiley, 2006.
Figure 2. Diagram of female meiosis to illustrate premature separation of chromatids. Two pairs of homologous chromosomes are shown, but one pair is not closely paired during prophase I of meiosis; this predisposes to early separation of the constituent chromatids of one of the unpaired chromosomes before the first anaphase. The separated chromatids can then migrate at random to the primary oocyte or first polar body, causing aneuploidy in the mature gamete. Reproduced from Human Cytogenetics, in Embryos, Genes and Birth Defects. eds Ferretti, Copp, Tickle and Moore, 2nd edn., Wiley, 2006.


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Further Reading

Delhanty JDA (2001) Preimplantation genetics: an explanation for poor human fertility? Annals of Human Genetics 65: 331–338.

Delhanty JDA (2007) Mechanisms of aneuploidy induction in oogenesis and early embryogenesis. Fetal & Maternal Medicine Review 18 (2): 85–101.

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Delhanty, Joy DA(Jul 2018) Origins of Human Aneuploidy. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021444.pub2]