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J Med Genet 48:433-437 doi:10.1136/jmg.2010.088070
  • Mutational mechanisms
  • Original article

Array comparative genomic hybridisation on first polar bodies suggests that non-disjunction is not the predominant mechanism leading to aneuploidy in humans

Editor's Choice
  1. D K Griffin1
  1. 1School of Biosciences, University of Kent, Canterbury, UK
  2. 2The London Bridge Fertility, Gynaecology and Genetics Centre, London, UK
  3. 3BlueGnome Limited, Mill Court, Great Shelford, Cambridge, UK
  1. Correspondence to D K Griffin, School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK; d.k.griffin{at}kent.ac.uk
  1. Contributors DKG, AHH, ART and AG designed and implemented the study. ASG, CSO, APCB and DKG interpreted the graphs. JT and KB performed the IVF and oocyte biopsy. ASG and APCB performed the array CGH. ASG and DKG wrote the manuscript with comments from all other authors.

  • Received 10 December 2010
  • Revised 29 March 2011
  • Accepted 30 March 2011
  • Published Online First 26 May 2011

Abstract

Introduction Aneuploidy (the presence of extra or missing chromosomes) arises primarily through chromosome segregation errors in the oocyte at meiosis I but the details of mechanism by which such errors occur in humans are the subject of some debate. It is generally believed that aneuploidy arises primarily as a result of segregation of a whole chromosome to the same pole as its homologue (non-disjunction). Nonetheless, classical cytogenetic studies suggest that this model does not fully account for the patterns observed in human oocytes. An alternative model (precocious separation of sister chromatids) has thus been proposed, but recurring criticism of this model purports that technical issues may have led to interpretation errors.

Materials and methods Array comparative genomic hybridisation (aCGH) was used on 164 human first polar bodies to distinguish between whole chromosome (non-disjunction) and chromatid (precocious separation) errors.

Results Single chromatid errors were over 11 times more common than whole chromosome errors, consistent with prior classical cytogenetic and fluorescence in situ hybridisation (FISH) studies.

Discussion The received wisdom that non-disjunction is the primary mechanism leading to human aneuploidy should be reconsidered.

Footnotes

  • Funding This work was funded, in part by a Career Development Fellowship (BB/E024211/1) awarded to DKG. Other funders: BBSRC.

  • Competing interests A Thornhill and A Handyside have, or have had, directorial roles in the London Bridge Centre. A Gordon is a director of BlueGnome. Both companies could, potentially, benefit indirectly from the publication of this article.

  • Ethics approval This study was conducted with the approval of the research licence held at the London Bridge Fertility, Gynaecology and Genetics Centre.

  • Provenance and peer review Not commissioned; externally peer reviewed.