De novo mutations in histone-modifying genes in congenital heart disease (original) (raw)

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Data deposits

Messenger RNA and protein sequences are available in the RefSeq database (http://www.ncbi.nlm.nih.gov/refseq/) under accession numbers listed in Supplementary Table 4; mutation data are available at dbSNP (http://www.ncbi.nlm.nih.gov/snp) under batch accession 1059065.

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Acknowledgements

The authors are grateful to the patients and families who participated in this research. We thank the following team members for contributions to patient recruitment: D. Awad, K. Celia, D. Etwaru, R. Korsin, A. Lanz, E. Marquez, J. K. Sond, A. Wilpers, R. Yee (Columbia Medical School); K. Boardman, J. Geva, J. Gorham, B. McDonough, A. Monafo, J. Stryker (Harvard Medical School); N. Cross (Yale School of Medicine); S. M. Edman, J. L. Garbarini, J. E. Tusi, S. H. Woyciechowski (Children’s Hospital of Philadelphia); J. Ellashek and N. Tran (Children’s Hospital of Los Angeles); K. Flack (University College London); D.Gruber, N. Stellato (Steve and Alexandra Cohen Children’s Medical Center of New York); D. Guevara, A. Julian, M. Mac Neal, C. Mintz (Icahn School of Medicine at Mount Sinai); and E. Taillie (University of Rochester School of Medicine and Dentistry). We also thank V. Spotlow, P. Candrea, K. Pavlik and M. Sotiropoulos for their expert production of exome sequences. We thank B. Bernstein and R. Ryan (Massachusetts General Hospital) and B. Bruneau (Gladstone Institute and University of California, San Francisco) for discussions. This work was supported by the National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) Pediatric Cardiac Genomics Consortium (U01-HL098188, U01-HL098147, U01-HL098153, U01-HL098163, U01-HL098123, U01-HL098162) and in part by the Simons Foundation for Autism Research and the NIH Centers for Mendelian Genomics (5U54HG006504).

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Author notes

1. Samir Zaidi and Murim Choi: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Genetics, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
   Samir Zaidi, Murim Choi, John D. Overton, Khalid A. Fakhro, Alexander Lopez, Shrikant M. Mane, Stephan J. Sanders, Mathew W. State, Irina R. Tikhonova, Hongyu Zhao, Martina Brueckner & Richard P. Lifton
2. Howard Hughes Medical Institute, Yale University, Connecticut, 06510, USA
   Samir Zaidi, Murim Choi, Khalid A. Fakhro & Richard P. Lifton
3. Department of Genetics, Harvard Medical School, Boston, 02115, Massachusetts, USA
   Hiroko Wakimoto, Jianming Jiang, Kerry K. Brown, Steve DePalma, Michael Parfenov, Jonathan G. Seidman & Christine E. Seidman
4. Department of Pediatrics, Columbia University Medical Center, New York, 10032, New York, USA
   Lijiang Ma, Teresa Lee, Dorothy Warburton, Ismee A. Williams & Wendy K. Chung
5. Howard Hughes Medical Institute, Harvard University, Boston, 02115, Massachusetts, USA
   Jianming Jiang & Christine E. Seidman
6. Yale Center for Mendelian Genomics, New Haven, 06510, Connecticut, USA
   John D. Overton, Alexander Lopez, Shrikant M. Mane, Irina R. Tikhonova & Richard P. Lifton
7. Yale Center for Genome Analysis, Yale University, New Haven, 06511, Connecticut, USA
   John D. Overton, Robert D. Bjornson, Nicholas J. Carriero, Alexander Lopez, Shrikant M. Mane, Irina R. Tikhonova & Richard P. Lifton
8. Steven and Alexandra Cohen Children’s Medical Center of New York, New Hyde Park, 11040, New York, USA
   Angela Romano-Adesman
9. Department of Computer Science, Yale University, New Haven, 06511, Connecticut, USA
   Robert D. Bjornson & Nicholas J. Carriero
10. Department of Cardiology, Children’s Hospital Boston, Boston, 02115, Massachusetts, USA
    Roger E. Breitbart, Jane W. Newburger & Amy E. Roberts
11. Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York 10032, USA,
    Yee Him Cheung
12. Department of Cardiology, University College London, Great Ormond Street Hospital, London, WC1N 3JH, UK
    John Deanfield & Juan Kaski
13. Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, USA
    Joseph Glessner & Hakon Hakonarson
14. Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA
    Hakon Hakonarson, Peter S. White & Elizabeth Goldmuntz
15. The Center for Biomedical Informatics, The Children’s Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, USA
    Michael J. Italia, Jeremy Leipzig, Wei Wang & Peter S. White
16. National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA
    Jonathan R. Kaltman
17. Section of Cardiothoracic Surgery, University of Southern California Keck School of Medicine, Los Angeles, 90089, California, USA
    Richard Kim
18. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, 10032, New York, USA
    Jennie K. Kline
19. Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, 77030, Texas, USA
    Laura E. Mitchell
20. Department of Computer Science, Columbia University, New York, 10032, New York, USA
    Itsik Pe’er
21. Department of Pediatrics, University of Rochester Medical Center, The School of Medicine and Dentistry, Rochester, 14611, New York, USA
    George Porter
22. Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA
    Ravi Sachidanandam, Sailakshmi Subramanian & Bruce D. Gelb
23. Department of Psychiatry, Program on Neurogenetics, Child Study Center, Yale University, New Haven, 06510, Connecticut, USA
    Stephan J. Sanders & Mathew W. State
24. Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA
    Howard S. Seiden & Bruce D. Gelb
25. Department of Computer Science, New Jersey Institute of Technology, Newark, 07102, New Jersey, USA
    Wei Wang
26. Department of Pathology, Columbia University Medical Center, New York, 10032, New Jersey, USA
    Dorothy Warburton
27. Department of Biostatistics, Yale School of Public Health, New Haven, 06510, Connecticut, USA
    Hongyu Zhao
28. Department of Pediatrics Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Martina Brueckner
29. Department of Medicine, Columbia University Medical Center, New York, 10032, New York, USA
    Wendy K. Chung
30. The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, 10029, New York, USA
    Bruce D. Gelb
31. Division of Cardiology, The Children’s Hospital of Philadelphia, The University of Pennsylvania Perelman School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Elizabeth Goldmuntz
32. Cardiovascular Division, Brigham & Women’s Hospital, Harvard University, Boston, 02115, Massachusetts, USA
    Christine E. Seidman
33. Department of Internal Medicine, Yale University School of Medicine, New Haven, 06510, Connecticut, USA
    Richard P. Lifton

Authors

1. Samir Zaidi
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2. Murim Choi
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3. Hiroko Wakimoto
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4. Lijiang Ma
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5. Jianming Jiang
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6. John D. Overton
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7. Angela Romano-Adesman
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8. Robert D. Bjornson
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9. Roger E. Breitbart
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10. Kerry K. Brown
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11. Nicholas J. Carriero
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12. Yee Him Cheung
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13. John Deanfield
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14. Steve DePalma
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15. Khalid A. Fakhro
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16. Joseph Glessner
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17. Hakon Hakonarson
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18. Michael J. Italia
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19. Jonathan R. Kaltman
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20. Juan Kaski
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21. Richard Kim
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22. Jennie K. Kline
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23. Teresa Lee
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24. Jeremy Leipzig
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25. Alexander Lopez
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26. Shrikant M. Mane
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27. Laura E. Mitchell
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28. Jane W. Newburger
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29. Michael Parfenov
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30. Itsik Pe’er
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31. George Porter
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32. Amy E. Roberts
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33. Ravi Sachidanandam
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34. Stephan J. Sanders
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35. Howard S. Seiden
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36. Mathew W. State
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37. Sailakshmi Subramanian
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38. Irina R. Tikhonova
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39. Wei Wang
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40. Dorothy Warburton
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41. Peter S. White
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42. Ismee A. Williams
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43. Hongyu Zhao
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44. Jonathan G. Seidman
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45. Martina Brueckner
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46. Wendy K. Chung
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47. Bruce D. Gelb
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48. Elizabeth Goldmuntz
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49. Christine E. Seidman
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50. Richard P. Lifton
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Contributions

Study design: M.B., W.K.C., B.D.G., E.G., H.H., J.R.K., R.P.L., L.E.M., J.G.S., C.E.S., D.W., P.S.W.; cohort ascertainment, phenotypic characterization and recruitment: R.E.B., M.B., W.K.C., J.D., B.D.G., E.G., J.K., R.K., T.L., J.W.N., G.P., A.R.-A., H.S.S., C.E.S., I.A.W.; informatics/data management: R.D.B., R.E.B., N.J.C., M.C., S.D., J.G., H.H., M.J.I., J.L., A.L., S.M.M., J.D.O., M.P., A.E.R., J.G.S., W.W., P.S.W., S.Z.; exome sequencing production: J.D.O., A.L., R.P.L., S.M.M., M.W.S., I.R.T.; de novo mutation validation: W.K.C., L.M.; exome sequencing analysis: K.K.B., Y.H.C., M.C., S.D., K.A.F., J.G., J.K.K., R.P.L., I.P., R.S., S.J.S., J.G.S., C.E.S., S.S., W.W., S.Z.; RNA sequence production/analysis: J.J., M.P., C.E.S., J.G.S., H.W.; statistical analysis: M.C., R.P.L., I.P., A.E.R., C.E.S., J.G.S., S.Z., H.Z.; writing of manuscript: M.B., M.C., W.K.C., B.D.G., E.G., J.R.K., R.P.L., C.E.S., S.Z. Co-senior authors: M.B., W.K.C., B.D.G., E.G., C.E.S. and R.P.L.

Corresponding authors

Correspondence toMartina Brueckner, Wendy K. Chung, Bruce D. Gelb, Elizabeth Goldmuntz, Christine E. Seidman or Richard P. Lifton.

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The authors declare no competing financial interests.

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Zaidi, S., Choi, M., Wakimoto, H. et al. De novo mutations in histone-modifying genes in congenital heart disease.Nature 498, 220–223 (2013). https://doi.org/10.1038/nature12141

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• Received: 16 January 2013
• Accepted: 02 April 2013
• Published: 12 May 2013
• Issue Date: 13 June 2013
• DOI: https://doi.org/10.1038/nature12141