@article{5e4fd76abf5e466c9271047059f0ecd0,
title = "A copy number variation morbidity map of developmental delay",
abstract = "To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that 1/414.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.",
author = "Cooper, {Gregory M.} and Coe, {Bradley P.} and Santhosh Girirajan and Rosenfeld, {Jill A.} and Vu, {Tiffany H.} and Carl Baker and Charles Williams and Heather Stalker and Rizwan Hamid and Vickie Hannig and Hoda Abdel-Hamid and Patricia Bader and Elizabeth McCracken and Dmitriy Niyazov and Kathleen Leppig and Heidi Thiese and Marybeth Hummel and Nora Alexander and Jerome Gorski and Jennifer Kussmann and Vandana Shashi and Krys Johnson and Catherine Rehder and Ballif, {Blake C.} and Shaffer, {Lisa G.} and Eichler, {Evan E.}",
note = "Funding Information: We thank N. Krumm, M. Malig, L. Vives and J. Luu for assistance in validation experiments. We also thank M. Dennis, C. Alkan, E. Karakoc 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/. Funding for the project was provided by the Wellcome Trust under awards 076113 and 085475. We also thank A. Aragaki, C. Kooperberg and R. Jackson for access to SNP data (Fred Hutchinson Cancer Research Center (FHCRC) control dataset) generated as part of the ongoing genome-wide association study to identify genetic components of hip fracture in the Women{\textquoteright}s Health Initiative. This work was supported by US National Institutes of Health HD065285 to E.E.E. E.E.E. is an investigator of the Howard Hughes Medical Institute.",
year = "2011",
month = sep,
doi = "10.1038/ng.909",
language = "English (US)",
volume = "43",
pages = "838--846",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "9",
}