Patterns and rates of exonic de novo mutations in autism spectrum disorders (original) (raw)

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Data deposits

Data included in this manuscript have been deposited at dbGaP under accession number phs000298.v1.p1 and is available for download at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id5phs000298.v1.p1.

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Acknowledgements

This work was directly supported by NIH grants R01MH089208 (M.J.D.), R01 MH089025 (J.D.B.), R01 MH089004 (G.D.S.), R01MH089175 (R.A.G.) and R01 MH089482 (J.S.S.), and supported in part by NIH grants P50 HD055751 (E.H.C.), RO1 MH057881 (B.D.) and R01 MH061009 (J.S.S.). Y.K., G.C. and S.Y. are Seaver Fellows, supported by the Seaver Foundation. We thank T. Lehner, A. Felsenfeld and P. Bender for their support and contribution to the project. We thank S. Sanders and M. State for discussions on the interpretation of de novo events. We thank D. Reich for comments on the abstract and message of the manuscript. We thank E. Lander and D. Altshuler for comments on the manuscript. We acknowledge the assistance of M. Potter, A. McGrew and G. Crockett without whom these studies would not be possible, and Center for Human Genetics Research resources: Computational Genomics Core, Genetic Studies Ascertainment Core and DNA Resources core, supported in part by NIH NCRR grant UL1 RR024975, and the Vanderbilt Kennedy Center for Research on Human Development (P30 HD015052). This work was supported in part by R01MH084676 (S.S.). We acknowledge the clinicians and organizations that contributed to samples used in this study and the particular support of the Mount Sinai School of Medicine, University of Illinois-Chicago, Vanderbilt University, the Autism Genetics Resource Exchange and the institutions of the Boston Autism Consortium. We acknowledge A. Estes and G. Dawson for patient collection/characterization. We acknowledge partial support from U54 HG003273 (R.A.G.) and U54 HG003067 (E. Lander). J.D.B., B.D., M.J.D., R.A.G., A.S., G.D.S. and J.S.S. are lead investigators in the Autism Sequencing Consortium (ASC). The ASC is comprised of groups sharing massively parallel sequencing data in autism. Finally, we are grateful to the many families, without whose participation this project would not have been possible.

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Authors and Affiliations

1. Department of Medicine, Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, 02114, Massachusetts, USA
   Benjamin M. Neale, Kaitlin E. Samocha, Elaine Lim, Elizabeth Rossin, Andrew Kirby, Menachem Fromer & Mark J. Daly
2. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, 02142, Massachusetts, USA
   Benjamin M. Neale, Kaitlin E. Samocha, Christine Stevens, Paz Polak, Jared Maguire, Benjamin F. Voight, Elaine Lim, Elizabeth Rossin, Andrew Kirby, Jason Flannick, Menachem Fromer, Khalid Shakir, Tim Fennell, Kiran Garimella, Eric Banks, Ryan Poplin, Stacey Gabriel, Mark DePristo, Shamil Sunyaev & Mark J. Daly
3. Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, 10029, New York, USA
   Yan Kou, Avi Ma’ayan & Ruth Dannenfelser
4. Seaver Autism Center for Research and Treatment, Mount Sinai School of Medicine, New York, 10029, New York, USA
   Yan Kou, Vladimir Makarov, Seungtai Yoon, Guiqing Cai, Jayon Lihm & Joseph D. Buxbaum
5. Department of Statistics, Carnegie Mellon University, Pittsburgh, 15232, Pennsylvania, USA
   Li Liu, Chad Schafer & Kathryn Roeder
6. Human Genome Sequencing Center, Baylor College of Medicine, Houston, 77030, Texas, USA
   Aniko Sabo, Uma Nagaswamy, Donna Muzny, Jeffrey G. Reid, Irene Newsham, Yuanqing Wu, Lora Lewis, Yi Han, Eric Boerwinkle & Richard A. Gibbs
7. Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA
   Chiao-Feng Lin, Li-San Wang, Evan T. Geller, Otto Valladares & Gerard D. Schellenberg
8. Department of Psychiatry, Mount Sinai School of Medicine, New York, 10029, New York, USA
   Vladimir Makarov, Seungtai Yoon, Guiqing Cai, Jayon Lihm & Joseph D. Buxbaum
9. Division of Genetics, Department of Medicine Brigham & Women's Hospital and Harvard Medical School, Boston, 02115, Massachusetts, USA
   Paz Polak & Shamil Sunyaev
10. Departments of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt Brain Institute, Vanderbilt University, Nashville, 37232, Tennessee, USA
    Emily L. Crawford, Nicholas G. Campbell & James S. Sutcliffe
11. Biostatistics Department and Computer Science Department, Johns Hopkins University, Baltimore, 21205, Maryland, USA
    Han Liu & Tuo Zhao
12. Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, 10029, New York, USA
    Omar Jabado, Zuleyma Peralta & Joseph D. Buxbaum
13. Department of Pharmacology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Benjamin F. Voight
14. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA,
    Jack R. Wimbish, Braden E. Boone & Shawn E. Levy
15. INSERM U952 and CNRS UMR 7224 and UPMC Univ Paris 06, Paris, 75005, France
    Catalina Betancur
16. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, 77030, Texas, USA
    Eric Boerwinkle
17. Friedman Brain Institute, Mount Sinai School of Medicine, New York, 10029, New York, USA
    Joseph D. Buxbaum
18. Department of Psychiatry, University of Illinois at Chicago, Chicago, 60608, Illinois, USA
    Edwin H. Cook Jr
19. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, 15213, Pennsylvania, USA
    Bernie Devlin

Authors

1. Benjamin M. Neale
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2. Yan Kou
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3. Li Liu
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4. Avi Ma’ayan
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5. Kaitlin E. Samocha
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6. Aniko Sabo
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7. Chiao-Feng Lin
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8. Christine Stevens
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9. Li-San Wang
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10. Vladimir Makarov
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11. Paz Polak
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12. Seungtai Yoon
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13. Jared Maguire
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14. Emily L. Crawford
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15. Nicholas G. Campbell
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16. Evan T. Geller
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17. Otto Valladares
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18. Chad Schafer
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19. Han Liu
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20. Tuo Zhao
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21. Guiqing Cai
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22. Jayon Lihm
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23. Ruth Dannenfelser
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24. Omar Jabado
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25. Zuleyma Peralta
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26. Uma Nagaswamy
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27. Donna Muzny
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28. Jeffrey G. Reid
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29. Irene Newsham
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30. Yuanqing Wu
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31. Lora Lewis
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32. Yi Han
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33. Benjamin F. Voight
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34. Elaine Lim
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35. Elizabeth Rossin
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36. Andrew Kirby
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37. Jason Flannick
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38. Menachem Fromer
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39. Khalid Shakir
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40. Tim Fennell
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41. Kiran Garimella
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42. Eric Banks
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43. Ryan Poplin
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44. Stacey Gabriel
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45. Mark DePristo
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46. Jack R. Wimbish
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47. Braden E. Boone
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48. Shawn E. Levy
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49. Catalina Betancur
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50. Shamil Sunyaev
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51. Eric Boerwinkle
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52. Joseph D. Buxbaum
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53. Edwin H. Cook Jr
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54. Bernie Devlin
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55. Richard A. Gibbs
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56. Kathryn Roeder
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57. Gerard D. Schellenberg
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58. James S. Sutcliffe
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59. Mark J. Daly
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Contributions

Laboratory work: A.S., C.St., G.C., O.J., Z.P., J.D.B., D.M., I.N., Y.W., L.L., Y.H., S.G., E.L.C., N.G.C. and E.T.G. Data processing: B.M.N., K.E.S., E.L., A.K., J.F., M.F., K.S., T.F., K.G., E.Ba., R.P., M.DeP., S.G., S.Y., V.M., J.L., J.D.B., A.S., C.St., U.N., J.G.R., J.R.W., B.E.B., S.E.L., C.F.L., L.S.W. and O.V. Statistical analysis: B.M.N., L.L., K.E.S., C.Sh., B.F.V., J.M., E.R., S.S., P.P., Y.K., A.M., R.D., C.-F.L., L.-S.W., H.L., T.Z., E.Bo., R.A.G., J.D.B., C.B., E.H.C., J.S.S., G.D.S., B.D., K.R. and M.J.D. Principal Investigators/study design: E.Bo., R.A.G., E.H.C., J.D.B., K.R., B.D., G.D.S., J.S.S. and M.J.D. Y.K., L.L., A.M., K.E.S., A.S. and C.-F.L. contributed equally to this work. E.Bo., J.D.B., E.H.C., B.D., R.A.G., K.R., G.D.S., J.S.S. and M.J.D. are lead investigators of the ARRA Autism Sequencing Collaboration.

Corresponding authors

Correspondence toJoseph D. Buxbaum, Kathryn Roeder or Mark J. Daly.

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The authors declare no competing financial interests.

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Neale, B., Kou, Y., Liu, L. et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders.Nature 485, 242–245 (2012). https://doi.org/10.1038/nature11011

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• Received: 13 September 2011
• Accepted: 06 March 2012
• Published: 04 April 2012
• Issue Date: 10 May 2012
• DOI: https://doi.org/10.1038/nature11011