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Nucleic Acids Research 2006 34(6):1912-1924; doi:10.1093/nar/gkl137
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Published online 5 April 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
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Article

Human centromeric alphoid domains are periodically homogenized so that they vary substantially between homologues. Mechanism and implications for centromere functioning

Gérard Roizès*

Institut de Génétique Humaine, UPR 1142, CNRS 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France

*Tel: +33 0 4 99 61 99 64; Fax: +33 0 4 99 61 99 01; Email: roizes{at}igh.cnrs.fr

Received January 25, 2006. Revised February 21, 2006. Accepted March 15, 2006.

Sequence analysis of alphoid repeats from human chromosomes 17, 21 and 13 reveals recurrent diagnostic variant nucleotides. Their combinations define haplotypes, with higher order repeats (HORs) containing identical or closely-related haplotypes tandemly arranged into separate domains. The haplotypes found on homologues can be totally different, while HORs remain 99.8% homogeneous both intrachromosomally and between homologues. These results support the hypothesis, never before demonstrated, that unequal crossovers between sister chromatids accumulate to produce homogenization and amplification into tandem alphoid repeats. I propose that the molecular basis of this involves the diagnostic variant nucleotides, which enable pairing between HORs with identical or closely-related haplotypes. Domains are thus periodically renewed to maintain high intrachromosomal and interhomologue homogeneity. The capacity of a domain to form an active centromere is maintained as long as neither retrotransposons nor significant numbers of mutations affect it. In the presented model, a chromosome with an altered centromere can be transiently rescued by forming a neocentromere, until a restored, fully-competent domain is amplified de novo or rehomogenized through the accumulation of unequal crossovers.


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