The origin, mechanisms, incidence and clinical consequences of chromosomal mosaicism in humans

Hum Reprod Update. Jul-Aug 2014;20(4):571-81. doi: 10.1093/humupd/dmu016. Epub 2014 Mar 25.


Background: Chromosomal mosaicism, the presence of two or more distinct cell lines, is prevalent throughout human pre- and post-implantation development and can lead to genetic abnormalities, miscarriages, stillbirths or live births. Due to the prevalence and significance of mosaicism in the human species, it is important to understand the origins, mechanisms and incidence of mosaicism throughout development.

Methods: Literature searches were conducted utilizing Pubmed, with emphasis on human pre- and post-implantation mosaicism.

Results: Mosaicism persists in two separate forms: general and confined. General mosaicism is routine during human embryonic growth as detected by preimplantation genetic screening at either the cleavage or blastocyst stage, leading to mosaicism within both the placenta and fetus proper. Confined mosaicism has been reported in the brain, gonads and placenta, amongst other places. Mosaicism is derived from a variety of mechanisms including chromosome non-disjunction, anaphase lagging or endoreplication. Anaphase lagging has been implicated as the main process by which mosaicism arises in the preimplantation embryo. Furthermore, mosaicism can be caused by any one of numerous factors from paternal, maternal or exogenous factors such as culture media or possibly controlled ovarian hyperstimulation during in vitro fertilization (IVF). Mosaicism has been reported in as high as 70 and 90% of cleavage- and blastocyst-stage embryos derived from IVF, respectively.

Conclusions: The clinical consequences of mosaicism depend on which chromosome is involved, and when and where an error occurs. Mitotic rescue of a meiotic error or a very early mitotic error will typically lead to general mosaicism while a mitotic error at a specific cell lineage point typically leads to confined mosaicism. The clinical consequences of mosaicism are dependent on numerous aspects, with the consequences being unique for each event.

Keywords: IVF; PGS; aneuploidy; chromosome; mosaicism.

Publication types

  • Review

MeSH terms

  • Blastocyst / physiology*
  • Cell Lineage / physiology
  • Chromosome Disorders / etiology*
  • Cleavage Stage, Ovum / physiology
  • Embryo Implantation / physiology
  • Embryonic Development / genetics*
  • Fathers
  • Fertilization in Vitro / adverse effects
  • Humans
  • Mosaicism
  • Mothers
  • Preimplantation Diagnosis / methods

Supplementary concepts

  • Mosaic variegated aneuploidy syndrome