A copy number variation morbidity map of developmental delay

Gregory M. Cooper, Bradley P. Coe, Santhosh Girirajan, Jill A. Rosenfeld, Tiffany H. Vu, Carl Baker, Charles Williams, Heather Stalker, Rizwan Hamid, Vickie Hannig, Hoda Abdel-Hamid, Patricia Bader, Elizabeth McCracken, Dmitriy Niyazov, Kathleen Leppig, Heidi Thiese, Marybeth Hummel, Nora Alexander, Jerome Gorski, Jennifer KussmannVandana Shashi, Krys Johnson, Catherine Rehder, Blake C. Ballif, Lisa G. Shaffer, Evan E. Eichler

Research output: Contribution to journalArticle

741 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)838-846
Number of pages9
JournalNature Genetics
Volume43
Issue number9
DOIs
StatePublished - Sep 1 2011

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Intellectual Disability
Exome
Morbidity
Gene Dosage
Genetic Heterogeneity
Disabled Children
Autistic Disorder
Epilepsy
Genome
Autism Spectrum Disorder
Datasets
Chromosome 17q21.31 Deletion Syndrome

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Cooper, G. M., Coe, B. P., Girirajan, S., Rosenfeld, J. A., Vu, T. H., Baker, C., ... Eichler, E. E. (2011). A copy number variation morbidity map of developmental delay. Nature Genetics, 43(9), 838-846. https://doi.org/10.1038/ng.909
Cooper, Gregory M. ; Coe, Bradley P. ; Girirajan, Santhosh ; Rosenfeld, Jill A. ; Vu, Tiffany H. ; Baker, Carl ; Williams, Charles ; Stalker, Heather ; Hamid, Rizwan ; Hannig, Vickie ; Abdel-Hamid, Hoda ; Bader, Patricia ; McCracken, Elizabeth ; Niyazov, Dmitriy ; Leppig, Kathleen ; Thiese, Heidi ; Hummel, Marybeth ; Alexander, Nora ; Gorski, Jerome ; Kussmann, Jennifer ; Shashi, Vandana ; Johnson, Krys ; Rehder, Catherine ; Ballif, Blake C. ; Shaffer, Lisa G. ; Eichler, Evan E. / A copy number variation morbidity map of developmental delay. In: Nature Genetics. 2011 ; Vol. 43, No. 9. pp. 838-846.
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Cooper, GM, Coe, BP, Girirajan, S, Rosenfeld, JA, Vu, TH, Baker, C, Williams, C, Stalker, H, Hamid, R, Hannig, V, Abdel-Hamid, H, Bader, P, McCracken, E, Niyazov, D, Leppig, K, Thiese, H, Hummel, M, Alexander, N, Gorski, J, Kussmann, J, Shashi, V, Johnson, K, Rehder, C, Ballif, BC, Shaffer, LG & Eichler, EE 2011, 'A copy number variation morbidity map of developmental delay', Nature Genetics, vol. 43, no. 9, pp. 838-846. https://doi.org/10.1038/ng.909

A copy number variation morbidity map of developmental delay. / Cooper, Gregory M.; Coe, Bradley P.; Girirajan, Santhosh; Rosenfeld, Jill A.; Vu, Tiffany H.; Baker, Carl; Williams, Charles; Stalker, Heather; Hamid, Rizwan; Hannig, Vickie; Abdel-Hamid, Hoda; Bader, Patricia; McCracken, Elizabeth; Niyazov, Dmitriy; Leppig, Kathleen; Thiese, Heidi; Hummel, Marybeth; Alexander, Nora; Gorski, Jerome; Kussmann, Jennifer; Shashi, Vandana; Johnson, Krys; Rehder, Catherine; Ballif, Blake C.; Shaffer, Lisa G.; Eichler, Evan E.

In: Nature Genetics, Vol. 43, No. 9, 01.09.2011, p. 838-846.

Research output: Contribution to journalArticle

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Cooper GM, Coe BP, Girirajan S, Rosenfeld JA, Vu TH, Baker C et al. A copy number variation morbidity map of developmental delay. Nature Genetics. 2011 Sep 1;43(9):838-846. https://doi.org/10.1038/ng.909