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Title: Genome-wide copy number profiling of single cells in S-phase reveals DNA-replication domains
Authors: Van der Aa, Niels
Cheng, Jiqiu
Mateiu, Ligia
Zamani Esteki, Masoud
Kumar, Parveen
Dimitriadou, Eftychia
Vanneste, Evelyne
Moreau, Yves
Vermeesch, Joris
Voet, Thierry # ×
Issue Date: Apr-2013
Publisher: Oxford University Press
Series Title: Nucleic acids research vol:41 issue:6
Article number: e66
Abstract: Single-cell genomics is revolutionizing basic genome research and clinical genetic diagnosis. However, none of the current research or clinical methods for single-cell analysis distinguishes between the analysis of a cell in G1-, S- or G2/M-phase of the cell cycle. Here, we demonstrate by means of array comparative genomic hybridization that charting the DNA copy number landscape of a cell in S-phase requires conceptually different approaches to that of a cell in G1- or G2/M-phase. Remarkably, despite single-cell whole-genome amplification artifacts, the log2 intensity ratios of single S-phase cells oscillate according to early and late replication domains, which in turn leads to the detection of significantly more DNA imbalances when compared with a cell in G1- or G2/M-phase. Although these DNA imbalances may, on the one hand, be falsely interpreted as genuine structural aberrations in the S-phase cell's copy number profile and hence lead to misdiagnosis, on the other hand, the ability to detect replication domains genome wide in one cell has important applications in DNA-replication research. Genome-wide cell-type-specific early and late replicating domains have been identified by analyses of DNA from populations of cells, but cell-to-cell differences in DNA replication may be important in genome stability, disease aetiology and various other cellular processes.
URI: 
ISSN: 0305-1048
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Reproductive Genomics
Laboratory for Cytogenetics and Genome Research
× corresponding author
# (joint) last author

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