Systematic biases in DNA copy number originate from isolation procedures

S. van Heesch, M. Mokry, V. Boskova, W. Junker, R. Mehon, P. Toonen, E. de Bruijn, J.D. Shull, T.J. Aitman, E. Cuppen, V. Guryev

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

34 Citaten (Scopus)


BACKGROUND: The ability to accurately detect DNA copy number variation in both a sensitive and quantitative manner is important in many research areas. However, genome-wide DNA copy number analyses are complicated by variations in detection signal. RESULTS: While GC content has been used to correct for this, here we show that coverage biases are tissue-specific and independent of the detection method as demonstrated by next-generation sequencing and array CGH. Moreover, we show that DNA isolation stringency affects the degree of equimolar coverage and that the observed biases coincide with chromatin characteristics like gene expression, genomic isochores, and replication timing. CONCLUSION: These results indicate that chromatin organization is a main determinant for differential DNA retrieval. These findings are highly relevant for germline and somatic DNA copy number variation analyses.
Originele taal-2Engels
Pagina's (van-tot)33
TijdschriftGenome Biology
Nummer van het tijdschrift4
StatusGepubliceerd - 2013


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