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First published online 12 February 2008
doi: 10.1242/jcs.025205

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Nuclear organisation in totipotent human nuclei and its relationship to chromosomal abnormality

¹ Department of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK
² The London Bridge Fertility, Gynaecology and Genetics Centre, 1 St Thomas Street, London Bridge, London, SE1 9RY, UK
³ Department of Obstetrics and Gynaecology, University College London, 86-96 Chenies Mews, London, WC1E 6HX, UK

^* Author for correspondence (e-mail: d.k.griffin{at}kent.ac.uk)

Accepted 4 December 2007

Studies of nuclear organisation, most commonly determining the nuclear location of chromosome territories and individual loci, have furthered our understanding of nuclear function, differentiation and disease. In this study, by examining eight loci on different chromosomes, we tested hypotheses that: (1) totipotent human blastomeres adopt a nuclear organisation akin to that of committed cells; (2) nuclear organisation is different in chromosomally abnormal blastomeres; and (3) human blastomeres adopt a `chromocentre' pattern. Analysis of in vitro fertilisation (IVF) conceptuses permits valuable insight into the cell biology of totipotent human nuclei. Here, extrapolations from images of preimplantation genetic screening (PGS) cases were used to make comparisons between totipotent blastomeres and several committed cells, showing some differences and similarities. Comparisons between chromosomally abnormal nuclei and those with no detected abnormality (NDA) suggest that the former display a significant non-random pattern for all autosomal loci, but there is a less distinct, possibly random, pattern in `NDA' nuclei. No evidence was found that the presence of an extra chromosome is accompanied by an altered nuclear location for that chromosome. Centromeric loci on chromosomes 15 and 16 normally seen at the nuclear periphery were mostly centrally located in aneuploid cells, providing some evidence of a `chromocentre'; however, the chromosome-18 centromere was more peripheral, similar to committed cells. Our results provide clues to the nature of totipotency in human cells and might have future applications for preimplantation diagnosis and nuclear transfer.

Key words: Nuclear organisation, Chromosome, Preimplantation human embryos

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