A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay (original) (raw)

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Acknowledgements

We thank the subjects and their families for participating in this study. We thank M. Whyte for providing cardiological evaluation (for case SG07). We thank A. Singleton, L. Ferrucci and R. Krauss for sharing the control CNV data generated with support from the Intramural Research Program of the National Institute on Aging, National Heart, Lung, and Blood Institute (PARC project), and the National Institutes of Health, Department of Health and Human Services. For the schizophrenia study, genotyping of samples was also provided through the genetic association information network (GAIN). Samples and associated phenotype data for the genome-wide association of schizophrenia study were provided by the Molecular Genetics of Schizophrenia Collaboration (principal investigator: P.V. Gejman, Evanston Northwestern Healthcare (ENH) and Northwestern University, Evanston, Illinois, USA). We also thank J. Smith for SNP genotyping; T. Louie for bioinformatics support; C. Campbell, L. Perez-Jurado, G. Kirov, M.K. Rudd and C. Lese-Martin for useful discussions; and T. Brown, P. Sudmant and J. Kitzman for critical review of the manuscript. This work was supported by NIH grant HD065285 (E.E.E.), a grant from the Simons Foundation (SFARI 137578 to E.E.E.) and a NARSAD Award (M.-C.K.). G.M.C. is supported by a Merck, Jane Coffin Childs Memorial Fund post-doctoral fellowship. E.E.E. is an investigator of the Howard Hughes Medical Institute.

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Author notes

1. Santhosh Girirajan and Jill A Rosenfeld: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA
   Santhosh Girirajan, Gregory M Cooper, Francesca Antonacci, Priscillia Siswara, Andy Itsara, Laura Vives, Carl Baker, Heather C Mefford, Jeffrey M Kidd, Diane E Dickel, Mary-Claire King & Evan E Eichler
2. Signature Genomic Laboratories, Spokane, Washington, USA
   Jill A Rosenfeld, Blake C Ballif & Lisa G Shaffer
3. Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA
   Tom Walsh & Mary-Claire King
4. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA
   Shane E McCarthy
5. Department of Statistics, Faculty of Science, The University of Auckland, Auckland, New Zealand
   Sharon R Browning & Brian L Browning
6. Psychology Research Laboratory, McLean Hospital, Belmont, Massachusetts, USA
   Deborah L Levy
7. Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
   Deborah L Levy & Lynn E DeLisi
8. Department of Pediatrics, Weisskopf Child Evaluation Center, University of Louisville, Louisville, Kentucky, USA
   Kathryn Platky, Gordon C Gowans, Jessica J Wetherbee & Alexander Asamoah
9. Division of Child Neurology, Department of Neurology, University of Louisville, School of Medicine, Louisville, Kentucky, USA
   Darren M Farber
10. Department of Medical and Molecular Genetics, School of Medicine, Indiana University, Indianapolis, Indiana, USA
    David D Weaver & Paul R Mark
11. Department of Neurology, Division of Pediatric Neurology, School of Medicine, Indiana University, Indianapolis, Indiana, USA
    Jennifer Dickerson & Bhuwan P Garg
12. Division of Genetics, Maine Medical Partners Pediatric Specialty Care, Maine Medical Center, Portland, Maine, USA
    Sara A Ellingwood, Rosemarie Smith, Valerie C Banks & Wendy Smith
13. Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina, USA
    Marie T McDonald
14. Department of Pediatrics, University of Toledo Medical College and Northwest Ohio Regional Genetics Center, Toledo, Ohio, USA
    Joe J Hoo & Beatrice N French
15. Medical Genetics, Shodair Children's Hospital, Helena, Montana, USA
    Cindy Hudson & John P Johnson
16. Division of Clinical Genetics, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
    Jillian R Ozmore & John B Moeschler
17. Magee-Womens Hospital of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
    Urvashi Surti
18. Medical Genetics and Neurodevelopmental Center, St. Vincent Children's Hospital, Indianapolis, Indiana, USA
    Luis F Escobar & Dima El-Khechen
19. Division of Medical Genetics, University of Missouri, Columbia, Missouri, USA
    Jerome L Gorski & Jennifer Kussmann
20. Geisinger Medical Center, Danville, Pennsylvania, USA
    Bonnie Salbert
21. Division of Genetics, Department of Pediatrics, Louisiana State University Health Sciences Center and Children's Hospital, New Orleans, Louisiana, USA
    Yves Lacassie
22. Department of Pediatrics and Genetics, University of Pennsylvania, and the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Alisha Biser, Donna M McDonald-McGinn, Elaine H Zackai, Matthew A Deardorff & Tamim H Shaikh
23. South Australian Clinical Genetics Service, South Australian Pathology at Women's and Children's Hospital, Adelaide, Australia
    Eric Haan
24. Department of Paediatrics, The University of Adelaide, Adelaide, Australia
    Eric Haan & Jozef Gécz
25. Genetics and Molecular Pathology, and South Australian Pathology at Women's and Children's Hospital, Adelaide, Australia
    Kathryn L Friend & Jozef Gécz
26. Oasi Institute for Research and Care in Mental Retardation and Brain Aging, Troina, Italy
    Marco Fichera & Corrado Romano
27. VA Boston Healthcare System, Brockton, Massachusetts, USA
    Lynn E DeLisi
28. Departments of Psychiatry and Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California, USA.,
    Jonathan Sebat
29. Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA
    Evan E Eichler

Authors

1. Santhosh Girirajan
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2. Jill A Rosenfeld
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3. Gregory M Cooper
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4. Francesca Antonacci
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5. Priscillia Siswara
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6. Andy Itsara
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7. Laura Vives
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8. Tom Walsh
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9. Shane E McCarthy
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10. Carl Baker
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11. Heather C Mefford
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12. Jeffrey M Kidd
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13. Sharon R Browning
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14. Brian L Browning
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15. Diane E Dickel
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16. Deborah L Levy
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17. Blake C Ballif
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18. Kathryn Platky
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19. Darren M Farber
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20. Gordon C Gowans
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21. Jessica J Wetherbee
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22. Alexander Asamoah
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23. David D Weaver
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24. Paul R Mark
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25. Jennifer Dickerson
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26. Bhuwan P Garg
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27. Sara A Ellingwood
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28. Rosemarie Smith
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29. Valerie C Banks
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30. Wendy Smith
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31. Marie T McDonald
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32. Joe J Hoo
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33. Beatrice N French
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34. Cindy Hudson
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35. John P Johnson
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36. Jillian R Ozmore
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37. John B Moeschler
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38. Urvashi Surti
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39. Luis F Escobar
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40. Dima El-Khechen
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41. Jerome L Gorski
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42. Jennifer Kussmann
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43. Bonnie Salbert
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44. Yves Lacassie
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45. Alisha Biser
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46. Donna M McDonald-McGinn
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47. Elaine H Zackai
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48. Matthew A Deardorff
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49. Tamim H Shaikh
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50. Eric Haan
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51. Kathryn L Friend
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52. Marco Fichera
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53. Corrado Romano
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54. Jozef Gécz
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55. Lynn E DeLisi
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56. Jonathan Sebat
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57. Mary-Claire King
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58. Lisa G Shaffer
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59. Evan E Eichler
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Contributions

This study was designed by S.G., L.G.S. and E.E.E. J.A.R., B.C.B. and L.G.S. supervised array-CGH experiments at Signature Genomics. J.A.R. coordinated clinical data collection. T.W., S.E.M., D.E.D., D.L.L., J.S., L.E.D. and M.-C.K. contributed to schizophrenia data collection and analysis. S.G., L.V. and C.B. performed high-density array-CGH experiments. G.M.C. and A.I. analyzed control CNV data. S.G., F.A. and J.M.K. performed genome structure analysis. F.A. performed FISH experiments. S.G. and P.S. sequenced and analyzed candidate genes. S.R.B. and B.L.B. performed haplotype analysis. K.P., D.M.F., G.C.G., J.J.W., A.A., D.D.W., P.R.M., J.D., B.P.G., S.A.E., R.S., V.C.B., W.S., M.T.M., J.J.H., B.N.F., C.H., J.P.J., J.R.O., J.B.M., U.S., L.F.E., D.E.-K., J.L.G., J.K., B.S., Y.L., A.B., D.M.M.-M., E.H.Z., M.A.D., T.H.S., E.H., K.L.F., M.F., C.R. and J.G. provided clinical information. H.C.M. provided 1q21.1 data. S.G., G.M.C., M.-C.K. and E.E.E. contributed to data interpretation. S.G. and E.E.E. wrote the manuscript.

Corresponding author

Correspondence toEvan E Eichler.

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Competing interests

E.E.E. is a member of the Scientific Advisory Board of Pacific Biosciences. J.A.R. and B.C.B. are employees of Signature Genomic Laboratories, LLC. L.G.S. is an employee of, owns shares in and sits on the Members' Board of Signature Genomic Laboratories, LLC.

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Girirajan, S., Rosenfeld, J., Cooper, G. et al. A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay.Nat Genet 42, 203–209 (2010). https://doi.org/10.1038/ng.534

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• Received: 21 October 2009
• Accepted: 15 January 2010
• Published: 14 February 2010
• Issue Date: March 2010
• DOI: https://doi.org/10.1038/ng.534