A copy number variation morbidity map of developmental delay
- PMID: 21841781
- PMCID: PMC3171215
- DOI: 10.1038/ng.909
A copy number variation morbidity map of developmental delay
Erratum in
- Nat Genet. 2014 Sep;46(9):1040
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 ∼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.
Conflict of interest statement
E.E.E. is a member of the Scientific Advisory Board of Pacific Biosciences. J.A.R., B.C.B., and L.G.S are employees of PerkinElmer.
Figures
Similar articles
-
Ohnologs are overrepresented in pathogenic copy number mutations.Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):361-6. doi: 10.1073/pnas.1309324111. Epub 2013 Dec 24. Proc Natl Acad Sci U S A. 2014. PMID: 24368850 Free PMC article.
-
The clinical benefit of array-based comparative genomic hybridization for detection of copy number variants in Czech children with intellectual disability and developmental delay.BMC Med Genomics. 2019 Jul 23;12(1):111. doi: 10.1186/s12920-019-0559-7. BMC Med Genomics. 2019. PMID: 31337399 Free PMC article.
-
Genetic and phenotypic analysis of 101 patients with developmental delay or intellectual disability using whole-exome sequencing.Clin Genet. 2021 Jul;100(1):40-50. doi: 10.1111/cge.13951. Epub 2021 Mar 8. Clin Genet. 2021. PMID: 33644862
-
Interpretation of array comparative genome hybridization data: a major challenge.Cytogenet Genome Res. 2011;135(3-4):222-7. doi: 10.1159/000334066. Epub 2011 Nov 12. Cytogenet Genome Res. 2011. PMID: 22086107 Review.
-
The array CGH and its clinical applications.Drug Discov Today. 2008 Sep;13(17-18):760-70. doi: 10.1016/j.drudis.2008.06.007. Epub 2008 Jul 17. Drug Discov Today. 2008. PMID: 18617013 Review.
Cited by
-
Impact and characterization of serial structural variations across humans and great apes.Nat Commun. 2024 Sep 13;15(1):8007. doi: 10.1038/s41467-024-52027-9. Nat Commun. 2024. PMID: 39266513 Free PMC article.
-
Centromeric transposable elements and epigenetic status drive karyotypic variation in the eastern hoolock gibbon.bioRxiv [Preprint]. 2024 Aug 30:2024.08.29.610280. doi: 10.1101/2024.08.29.610280. bioRxiv. 2024. PMID: 39257810 Free PMC article. Preprint.
-
Rare genomic copy number variants implicate new candidate genes for bicuspid aortic valve.PLoS One. 2024 Sep 6;19(9):e0304514. doi: 10.1371/journal.pone.0304514. eCollection 2024. PLoS One. 2024. PMID: 39240962 Free PMC article.
-
Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype.Hum Genomics. 2024 Sep 4;18(1):95. doi: 10.1186/s40246-024-00662-0. Hum Genomics. 2024. PMID: 39232803 Free PMC article.
-
Prenatal diagnosis of fetuses with 15q11.2 BP1-BP2 microdeletion in the Chinese population: a seven-year single-center retrospective study.Mol Cytogenet. 2024 Sep 2;17(1):20. doi: 10.1186/s13039-024-00690-4. Mol Cytogenet. 2024. PMID: 39218907 Free PMC article.
References
-
- Walsh T, et al. Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia. Science. 2008;320:539–43. - PubMed
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases