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Human Molecular Genetics Advance Access published online on November 25, 2003

Human Molecular Genetics, doi:10.1093/hmg/ddh016
© 2003 by Oxford University Press
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©2003 Oxford University Press

Article

Replication Timing of the Human Genome

Kathryn Woodfine 1, Heike Fiegler 1, David M. Beare 1, John E. Collins 1, Owen T. McCann 1, Bryan D. Young 2, Silvana Debernardi 2, Richard Mott 3, Ian Dunham 1, and Nigel P. Carter 1*

1 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA
2 Cancer Research UK, Molecular Oncology Group, Medical Oncology Unit, St Bartholomew's Hospital, London UK
3 Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford UK

* To whom correspondence should be addressed. E-mail: npc{at}sanger.ac.uk.


   Abstract

We have developed a directly quantitative method utilizing genomic clone DNA microarrays to assess the replication timing of sequences during the S phase of the cell cycle. The genomic resolution of the replication timing measurements is limited only by the genomic clone size and density. We demonstrate the power of this approach by constructing a genome wide map of replication timing in human lymphoblastoid cells using an array with clones spaced at 1 Mb intervals and a high resolution replication timing map of 22q with an array utilizing overlapping sequencing tile path clones. We show a positive correlation, both genome wide and at a high resolution, between replication timing and a range of genome parameters including GC content, gene density and transcriptional activity.


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