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Human Molecular Genetics Advance Access originally published online on November 25, 2003
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Human Molecular Genetics, 2004, Vol. 13, No. 2 191-202
DOI: 10.1093/hmg/ddh016

Replication timing of the human genome

Kathryn Woodfine1, Heike Fiegler1, David M. Beare1, John E. Collins1, Owen T. McCann1, Bryan D. Young2, Silvana Debernardi2, Richard Mott3, Ian Dunham1 and Nigel P. Carter1,*

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

Received September 5, 2003; Revised October 30, 2003; Accepted November 9, 2003

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.

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


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