Refining analyses of copy number variation identifies specific genes associated with developmental delay

BP Coe; K Witherspoon; JA Rosenfeld; BWM van Bon; AT Vulto-van Silfhout; P Bosco; KL Friend; C Baker; S Buono; LELM Vissers; JH Schuurs-Hoeijmakers; A Hoischen; R Pfundt; N Krumm; GL Carvill; D Li; D Amaral; N Brown; PJ Lockhart; IE Scheffer; A Alberti; M Shaw; R Pettinato; R Tervo; N de Leeuw; MRF Reijnders; BS Torchia; H Peeters; E Thompson; BJ O'Roak; M Fichera; JY Hehir-Kwa; J Shendure; HC Mefford; E Haan; J Gécz; BBA de Vries; C Romano; EE Eichler

Journal article

Refining analyses of copy number variation identifies specific genes associated with developmental delay

BP Coe, K Witherspoon, JA Rosenfeld, BWM van Bon, AT Vulto-van Silfhout, P Bosco, KL Friend, C Baker, S Buono, LELM Vissers, JH Schuurs-Hoeijmakers, A Hoischen, R Pfundt, N Krumm, GL Carvill, D Li, D Amaral, N Brown, PJ Lockhart, IE Scheffer Show all

Nature Genetics | Published : 2014

DOI: 10.1038/ng.3092

Abstract

© 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.Copy number variants (CNVs) are associated with many neurocognitive disorders; however, these events are typically large, and the underlying causative genes are unclear. We created an expanded CNV morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. We resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls. An integrated analysis of CNV and single-nucleotide variant (SNV) data pinpointed 10 genes enriched for putative loss of function. Follow-up of a subset of a..

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University of Melbourne Researchers

Paul Lockhart Author

Ingrid Scheffer Author

Grants

Awarded by National Institutes of Health

Funding Acknowledgements

We thank E Hormozdiari, M. Dennis and T. Brown for useful discussions and for editing the manuscript. B.P.C. is supported by a fellowship from the Canadian Institutes of Health Research. This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/. JAR. and B.S.T. are employees of Signature Genomics Laboratories, LLC, a subsidiary of PerkinElmer, Inc. This work was supported by US National Institute of Mental Health grant MH101221 and Paul G. Allen Family Foundation Award 11631 to E.E.E. E.E.E. is an Allen Distinguished Investigator and an investigator of the Howard Hughes Medical Institute.