A Copy Number Variation Morbidity Map of Developmental Delay

By Gregory M. Cooper, Bradley P. Coe, S. Girirajan, J. Rosenfeld, Tiffany H. Vu, Carl A. Baker, C. Williams, H. Stalker, R. Hamid, V. Hannig and 16 more. Nature Genetics, 2011

1,344 citations recorded by the source corpus.

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 ∼14.2% 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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/193f7fa4fdc0857775db94bf88ad03906baa6175

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Citations in the corpus

Quantifying penetrance in a dominant disease gene using large population control cohorts (2016, positive): “1%) diseases, and point estimates of the penetrance of individual variants have been limited to large copy number variations (8, 11).”
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