Refining analyses of copy number variation identifies specific genes associated with developmental delay (original) (raw)

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Acknowledgements

We thank F. Hormozdiari, M. Dennis and T. Brown for useful discussions and for editing the manuscript. B.P.C. is supported by a fellowship from the Canadian Institutes of Health Research. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/. J.A.R. and B.S.T. are employees of Signature Genomics Laboratories, LLC, a subsidiary of PerkinElmer, Inc. This work was supported by US National Institute of Mental Health grant MH101221 and Paul G. Allen Family Foundation Award 11631 to E.E.E. E.E.E. is an Allen Distinguished Investigator and an investigator of the Howard Hughes Medical Institute.

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Author notes

1. Brian J O'Roak & Marco Fichera
   Present address: Present addresses: Molecular and Medical Genetics, Oregon Health and Science University (OHSU), Portland, Oregon, USA (B.J.O.) and Medical Genetics, University of Catania, Catania, Italy (M.F.).,

Authors and Affiliations

1. Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA
   Bradley P Coe, Kali Witherspoon, Carl Baker, Nik Krumm, Brian J O'Roak, Jay Shendure & Evan E Eichler
2. Signature Genomics Laboratories, LLC, PerkinElmer, Inc., Spokane, Washington, USA
   Jill A Rosenfeld & Beth S Torchia
3. Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands
   Bregje W M van Bon, Anneke T Vulto-van Silfhout, Lisenka E L M Vissers, Janneke H Schuurs-Hoeijmakers, Alex Hoischen, Rolph Pfundt, Nicole de Leeuw, Margot R F Reijnders, Jayne Y Hehir-Kwa & Bert B A de Vries
4. SA Pathology, North Adelaide, South Australia, Australia
   Bregje W M van Bon, Kathryn L Friend, Marie Shaw, Elizabeth Thompson, Eric Haan & Jozef Gécz
5. IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Associazione Oasi Maria Santissima, Troina, Italy
   Paolo Bosco, Serafino Buono, Antonino Alberti, Rosa Pettinato, Marco Fichera & Corrado Romano
6. Department of Pediatrics, University of Washington, Seattle, Washington, USA
   Gemma L Carvill & Heather C Mefford
7. Representing the Autism Phenome Project, MIND Institute, University of California, Davis, Sacramento, California, USA
   Deana Li & David Amaral
8. Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia
   Natasha Brown & Paul J Lockhart
9. Barwon Child Health Unit, Barwon Health, Geelong, Victoria, Australia
   Natasha Brown
10. Murdoch Childrens Research Institute, University of Melbourne, Royal Children's Hospital, Melbourne, Victoria, Australia
    Paul J Lockhart
11. Florey Institute, University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Victoria, Australia
    Ingrid E Scheffer
12. Division of Developmental and Behavioral Pediatrics, Mayo Clinic, Rochester, Minnesota, USA
    Raymond Tervo
13. Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium
    Hilde Peeters
14. Leuven Autism Research (LAuRes), Leuven, Belgium
    Hilde Peeters
15. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia
    Elizabeth Thompson & Eric Haan
16. Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia
    Jozef Gécz
17. Howard Hughes Medical Institute, Seattle, Washington, USA
    Evan E Eichler

Authors

1. Bradley P Coe
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2. Kali Witherspoon
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3. Jill A Rosenfeld
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4. Bregje W M van Bon
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5. Anneke T Vulto-van Silfhout
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6. Paolo Bosco
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7. Kathryn L Friend
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8. Carl Baker
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9. Serafino Buono
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10. Lisenka E L M Vissers
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11. Janneke H Schuurs-Hoeijmakers
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12. Alex Hoischen
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13. Rolph Pfundt
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14. Nik Krumm
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15. Gemma L Carvill
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16. Deana Li
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17. David Amaral
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18. Natasha Brown
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19. Paul J Lockhart
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20. Ingrid E Scheffer
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21. Antonino Alberti
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22. Marie Shaw
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23. Rosa Pettinato
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24. Raymond Tervo
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25. Nicole de Leeuw
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26. Margot R F Reijnders
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27. Beth S Torchia
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28. Hilde Peeters
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29. Elizabeth Thompson
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30. Brian J O'Roak
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31. Marco Fichera
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32. Jayne Y Hehir-Kwa
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33. Jay Shendure
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34. Heather C Mefford
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35. Eric Haan
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36. Jozef Gécz
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37. Bert B A de Vries
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38. Corrado Romano
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39. Evan E Eichler
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Contributions

B.P.C. and E.E.E. designed the study. B.P.C. performed the data analysis. B.P.C., K.W. and C.B. performed array CGH, MIP sequencing and Sanger validation. J.A.R. and B.S.T. supervised array CGH experiments and coordinated clinical data collection at Signature Genomics. B.W.M.v.B., A.T.V.-v.S., P.B., K.L.F., S.B., L.E.L.M.V., J.H.S.-H., A.H., D.L., D.A., N.B., P.J.L., I.E.S., A.A., R. Pettinato, R.T., N.d.L., M.R.F.R., H.P., E.T., M.F., M.S., H.C.M., E.H., C.R., J.G. and B.B.A.d.V. provided clinical samples for resequencing, clinical reports and inheritance testing. J.Y.H.-K., R. Pfundt and N.d.L. curated the Nijmegen de novo CNV calls. B.P.C., K.W., C.B., B.J.O., J.S., and E.E.E. designed the MIP gene panel. G.L.C. and H.C.M. identified two SETBP1 variants in an independent screen. N.K. curated published de novo mutations. B.P.C. and E.E.E. wrote the manuscript. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence toEvan E Eichler.

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Competing interests

J.A.R. and B.S.T. are employees of Signature Genomics Laboratories, LLC, a subsidiary of PerkinElmer, Inc. E.E.E. is on the scientific advisory board (SAB) of DNAnexus, Inc., and was an SAB member of Pacific Biosciences, Inc. (2009–2013) and SynapDx Corp. (2011–2013).

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Coe, B., Witherspoon, K., Rosenfeld, J. et al. Refining analyses of copy number variation identifies specific genes associated with developmental delay.Nat Genet 46, 1063–1071 (2014). https://doi.org/10.1038/ng.3092

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• Received: 11 April 2014
• Accepted: 20 August 2014
• Published: 14 September 2014
• Issue Date: October 2014
• DOI: https://doi.org/10.1038/ng.3092