Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome (original) (raw)

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Acknowledgements

The authors would like to thank all participating families and clinicians, particularly J. Flint, P. Bolton, A. Clarke, C. Fairhurst, T. Wolff, S. Mansour, S. Holder, R. Gibbons, L. Brueton, P. Day, F. Stewart, S. Keane, N. Meston, A. Seller, P. Clouston and K. Smith. This work was supported by grants from the US National Institutes of Health (NIH) (HD043569; E.E.E.), Merck Research Laboratories (A.J.S.), The Health Foundation (S.J.L.K.) and the Oxford Genetics Knowledge Park (S.J.L.K., R.R., C.G.). E.E.E. is an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations

1. Department of Genome Sciences and The Howard Hughes Medical Institute, University of Washington School of Medicine, 1705 NE Pacific St., Seattle, 98195, Washington, USA
   Andrew J Sharp, Sierra Hansen, Ze Cheng & Evan E Eichler
2. NimbleGen Systems, Inc., Madison, 53711, Wisconsin, USA
   Rebecca R Selzer, Todd A Richmond & Peggy S Eis
3. Oxford Genetics Knowledge Park, The Wellcome Trust Centre for Human Genetics, Churchill Hospital, Oxford, OX3 7BN, UK
   Regina Regan, Cheryl Guiver & Samantha J L Knight
4. Department of Clinical Genetics, Oxford Radcliffe Hospitals National Health Service (NHS) Trust, Churchill Hospital, Oxford, OX3 7LJ, UK
   Jane A Hurst, Helen Stewart, Sue M Price & Edward Blair
5. Clinical and Molecular Genetics Unit, Institute of Child Health, University College London, London, UK
   Raoul C Hennekam
6. Department of Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
   Raoul C Hennekam
7. Department of Human Genetics, University of Chicago, Chicago, 60637, Illinois, USA
   Carrie A Fitzpatrick & Stuart Schwartz
8. Comprehensive Cancer Center, University of California San Francisco (UCSF), San Francisco, 94143, California, USA
   Rick Segraves, Donna G Albertson & Daniel Pinkel
9. Cancer Research Institute, UCSF, San Francisco, 94143, California, USA
   Donna G Albertson

Authors

1. Andrew J Sharp
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2. Sierra Hansen
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3. Rebecca R Selzer
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4. Ze Cheng
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5. Regina Regan
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6. Jane A Hurst
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7. Helen Stewart
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8. Sue M Price
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9. Edward Blair
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10. Raoul C Hennekam
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11. Carrie A Fitzpatrick
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12. Rick Segraves
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13. Todd A Richmond
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14. Cheryl Guiver
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15. Donna G Albertson
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16. Daniel Pinkel
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17. Peggy S Eis
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18. Stuart Schwartz
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19. Samantha J L Knight
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20. Evan E Eichler
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Contributions

This study was coordinated by A.J.S., P.S.E., S.S., S.J.L. and E.E.E.; the manuscript was written by A.J.S. and E.E.E.; experimental work was performed by A.J.S., S.H., R.R.S., R.R., C.A.F., R.S. and C.G.; clinical work was performed by J.A.H., H.S., S.M.P., E.B. and R.C.H.; computational analysis was performed by Z.C.; and array production was performed by T.A.R., D.G.A. and D.P.

Corresponding author

Correspondence toEvan E Eichler.

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Competing interests

P.S.E., R.R.S. and T.A.R. are employees of NimbleGen Systems, Inc. and have stock options in the company.

Supplementary information

Supplementary Fig. 1

FISH validation of 13 rearrangements detected using the SD BAC array. (PDF 1361 kb)

Supplementary Fig. 2

Parental origin and inversion analysis of the 17q21.31 deletion in the family of IMR103. (PDF 1588 kb)

Supplementary Table 1

A non-redundant set of 130 potential rearrangement hotspots in the human genome. (PDF 46 kb)

Supplementary Table 2

Copy number variations detected in 269 HapMap samples and in 290 patients with mental retardation using the SD BAC array. (PDF 3016 kb)

Supplementary Table 3

Nine additional rearrangements, including seven of uncertain significance, detected using the SD BAC array in 290 patients with mental retardation. (PDF 16 kb)

Supplementary Table 4

Comparison of phenotypes between four of the five cases of del 17q21.31 ascertained using the SD BAC array and three previously reported overlapping deletions, plus phenotype details of six further pathogenic rearrangements ascertained using the SD BAC array. (PDF 16 kb)

Supplementary Table 5

Segmental duplication clusters at five rearragement breakpoints as defined by high-density oligonucleotide array analysis. (PDF 21 kb)

Supplementary Table 6

PCR primers used in this study. (PDF 8 kb)

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Sharp, A., Hansen, S., Selzer, R. et al. Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome.Nat Genet 38, 1038–1042 (2006). https://doi.org/10.1038/ng1862

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• Received: 15 May 2006
• Accepted: 20 July 2006
• Published: 13 August 2006
• Issue Date: 01 September 2006
• DOI: https://doi.org/10.1038/ng1862