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We have systematically compared copy number variant (CNV) detection on eleven microarrays to evaluate data quality and CNV calling, reproducibility, concordance across array platforms and laboratory sites, breakpoint accuracy and analysis tool variability. Different analytic tools applied to the same raw data typically yield CNV calls with <50% concordance. Moreover, reproducibility in replicate experiments is <70% for most platforms. Nevertheless, these findings should not preclude detection of large CNVs for clinical diagnostic purposes because large CNVs with poor reproducibility are found primarily in complex genomic regions and would typically be removed by standard clinical data curation. The striking differences between CNV calls from different platforms and analytic tools highlight the importance of careful assessment of experimental design in discovery and association studies and of strict data curation and filtering in diagnostics. The CNV resource presented here allows independent data evaluation and provides a means to benchmark new algorithms.

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  • 29 May 2011

    In the version of this article initially published online, Bhooma Thiruvahindrapuram’s name was misspelled. The error has been corrected for the print, PDF and HTML versions of this article.


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We thank J. Rickaby and M. Lee for excellent technical assistance. We thank colleagues at Affymetrix, Agilent, Illumina and NimbleGen, and Biodiscovery for sharing data, sharing software and technical assistance. The Toronto Centre for Applied Genomics at the Hospital for Sick Children is acknowledged for database, technical assistance and bioinformatics support. This work was supported by funding from the Genome Canada/Ontario Genomics Institute, the Canadian Institutes of Health Research (CIHR), the McLaughlin Centre, the Canadian Institute of Advanced Research, the Hospital for Sick Children (SickKids) Foundation, a Broad SPARC Project award to P.K.D. and C.L., US National Institutes of Health (NIH) grant HD055150 to P.K.D., and the Department of Pathology at Brigham and Women's Hospital in Boston and NIH grants HG005209, HG004221 and CA111560 to C.L. N.P.C., D. Rajan, D. Rigler, T.F., S.G. and E.P. are supported by the Wellcome Trust (grant no. WT077008). D.P. is supported by fellowships from the Canadian Institutes of Health Research (no. 213997) and the Netherlands Organization for Scientific Research (Rubicon 825.06.031). X.S. is supported by a T32 Harvard Medical School training grant, and K.N. is supported by a T32 institutional training grant (HD007396). S.W.S. holds the GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the University of Toronto and the Hospital for Sick Children (Canada). L.F. is supported by the Göran Gustafsson Foundation and the Swedish Foundation for Strategic Research.

Author information

Author notes

    • Ji Hyeon Park

    Present address: Department of Obstetrics and Gynecology, Pochon CHA University College of Medicine, Seoul, South Korea.

    • Dalila Pinto
    •  & Katayoon Darvishi

    These authors contributed equally to this work.


  1. The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.

    • Dalila Pinto
    • , Anath C Lionel
    • , Bhooma Thiruvahindrapuram
    • , Jeffrey R MacDonald
    • , Aparna Prasad
    •  & Stephen W Scherer
  2. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Katayoon Darvishi
    • , Xinghua Shi
    • , Ryan Mills
    • , Kristin Noonan
    • , Richard S Smith
    • , Ji Hyeon Park
    •  & Charles Lee
  3. Wellcome Trust, Sanger Institute, Hinxton, Cambridge, UK.

    • Diana Rajan
    • , Diane Rigler
    • , Tom Fitzgerald
    • , Susan Gribble
    • , Elena Prigmore
    • , Matthew E Hurles
    •  & Nigel P Carter
  4. Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Kristin Noonan
    •  & Patricia K Donahoe
  5. McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Canada.

    • Stephen W Scherer
  6. Department of Immunology, Genetics and Pathology, SciLifeLab Uppsala, Rudbeck Laboratory, Uppsala University, Sweden.

    • Lars Feuk


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D.P., C.L., N.P.C., M.E.H., S.W.S. and L.F. conceived and designed the study. D.P. and L.F. coordinated sample distribution, experiments and analysis. K.D. managed the experiments conceived at the Harvard Medical School and performed the Nexus analysis. R.S.S., D. Rajan, D. Rigler, T.F., J.H.P., K.N., S.G. and E.P. performed the experiments. Data analyses were performed by D.P., K.D., R.S.S., D. Rajan, T.F., A.C.L., B.T., J.R.M., R.M., A.P., K.N., X.S., P.K.D. and L.F. All authors participated in discussions of different parts of the study. D.P., C.L., S.W.S. and L.F. wrote the manuscript. All authors read and approved the manuscript.

Competing interests

The authors declare competing interests. Affymetrix, Agilent, Illumina and Nimblegen provided arrays or reagents for use in this study at substantial discount. The Centre for Applied Genomics (TCAG) routinely provides fee-for-service experimentation using products from Affymetrix, Agilent and Illumina, and is a Core Lab for Affymetrix and Illumina. S.W.S. belongs to the Scientific Advisory Board of Combimatrix Diagnostics.

Corresponding author

Correspondence to Lars Feuk.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Methods, Supplementary Tables 1, 2, 4–6, and Supplementary Figs. 1–15

Excel files

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    Supplementary Table 3

    List of all CNVs that passed QC.

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