High-resolution mapping and analysis of copy number variations in the human genome: A data resource for clinical and research applications

  1. Tamim H. Shaikh1,2,11,
  2. Xiaowu Gai3,11,
  3. Juan C. Perin3,
  4. Joseph T. Glessner4,
  5. Hongbo Xie3,
  6. Kevin Murphy5,
  7. Ryan O'Hara3,
  8. Tracy Casalunovo4,
  9. Laura K. Conlin1,
  10. Monica D'Arcy5,
  11. Edward C. Frackelton4,
  12. Elizabeth A. Geiger1,
  13. Chad Haldeman-Englert1,
  14. Marcin Imielinski4,
  15. Cecilia E. Kim4,
  16. Livija Medne1,
  17. Kiran Annaiah4,
  18. Jonathan P. Bradfield4,
  19. Elvira Dabaghyan4,
  20. Andrew Eckert4,
  21. Chioma C. Onyiah4,
  22. Svetlana Ostapenko3,
  23. F. George Otieno4,
  24. Erin Santa4,
  25. Julie L. Shaner4,
  26. Robert Skraban4,
  27. Ryan M. Smith4,
  28. Josephine Elia6,7,
  29. Elizabeth Goldmuntz2,9,
  30. Nancy B. Spinner1,2,
  31. Elaine H. Zackai1,2,
  32. Rosetta M. Chiavacci4,
  33. Robert Grundmeier2,3,8,
  34. Eric F. Rappaport3,
  35. Struan F.A. Grant1,2,4,
  36. Peter S. White2,3,5,12 and
  37. Hakon Hakonarson1,2,4,10,12
  1. 1 Division of Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  2. 2 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
  3. 3 Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  4. 4 Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  5. 5 Division of Oncology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  6. 6 Department of Child and Adolescent Psychiatry, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  7. 7 Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA;
  8. 8 Division of General Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  9. 9 Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA;
  10. 10 Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA

    1. ↵11 These authors contributed equally to this work.

    Abstract

    We present a database of copy number variations (CNVs) detected in 2026 disease-free individuals, using high-density, SNP-based oligonucleotide microarrays. This large cohort, comprised mainly of Caucasians (65.2%) and African-Americans (34.2%), was analyzed for CNVs in a single study using a uniform array platform and computational process. We have catalogued and characterized 54,462 individual CNVs, 77.8% of which were identified in multiple unrelated individuals. These nonunique CNVs mapped to 3272 distinct regions of genomic variation spanning 5.9% of the genome; 51.5% of these were previously unreported, and >85% are rare. Our annotation and analysis confirmed and extended previously reported correlations between CNVs and several genomic features such as repetitive DNA elements, segmental duplications, and genes. We demonstrate the utility of this data set in distinguishing CNVs with pathologic significance from normal variants. Together, this analysis and annotation provides a useful resource to assist with the assessment of CNVs in the contexts of human variation, disease susceptibility, and clinical molecular diagnostics.

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    1. Published in Advance July 10, 2009, doi: 10.1101/gr.083501.108 Genome Res. 19: 1682-1690 Copyright © 2009 by Cold Spring Harbor Laboratory Press

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