Copy number variation

Author: A. Veltman
Submitted: Saturday 25th of September 2010 08:20:19 AM
Submitted by: egf
Educational levels: expert, qc3


Structural chromosomal rearrangements can lead to a wide variety of serious clinical manifestations, including mental retardation, schizophrenia and autism. Over the last years, chromosomal rearrangements below the detection level of conventional karyotyping have proven to contribute significantly to the cause of these neurodevelopmental and psychiatric diseases. These so-called copy number variations (CNVs) are now routinely being detected using various high-resolution microarray platforms targeting the entire human genome. In addition to their clinical diagnostic use, the introduction of these high-resolution platforms has facilitated identification of novel microdeletion and microduplication syndromes as well as disease genes. However, genotype-phenotype relationships are often complex, and this also is the case for more and more CNVs; a CNV may show extensive clinical variability between individuals, even within a single family. In this presentation I will address several aspects of copy number variations, ranging from CNV identification to interpretation, using mental retardation as a model disease. References 4. Hehir-Kwa JY, Wieskamp N, Webber C, Pfundt R, Brunner HG, Gilissen C,de Vries BBA, Ponting CP, Veltman JA. Accurate distinction of pathogenic from benign CNVs in Mental Retardation. PLoS Computational Biology, in press. 5. Vissers LE, de Vries BB, Veltman JA. Genomic microarrays in mental retardation: from CNV to gene, from research to diagnosis. Journal Medical Genetics 2009 Nov 30. [Epub ahead of print] 6. Veltman JA, Brunner HG. Understanding variable expressivity in microdeletion syndromes. Nature Genetics 42:192-3 (2010). 7. Vissers LELM, Bhatt SS, Janssen IM, Xia Z, Lalani SR, Pfundt R, Derwinska K, de Vries BBA, Gilissen C, Hoischen A, Nesteruk M, Wisniowiecka-Kowalnik B, Smyk M, Brunner HG, Cheung SW, Geurts van Kessel A, Veltman JA, Stankiewicz P. Rare pathogenic microdeletions and tandem duplications are microhomology-mediated and stimulated by local genomic architecture. Human Molecular Genetics 18:3579-93 (2009). 8. Webber C, Hehir-Kwa JY, Nguyen DQ, de Vries BBA, Veltman JA, Ponting CP. Forging links between human mental retardation-associated CNVs and mouse gene knockout models. PLoS Genetics 5: e1000531 (2009). 9. Koolen DA, Pfundt R, de Leeuw N, Hehir-Kwa JY, Nillesen WM, Neefs I, Scheltinga I, Sistermans E, Smeets D, Brunner HG, Geurts van Kessel A, Veltman JA, de Vries BBA. Genomic microarrays in mental retardation: a practical workflow for diagnostic applications. Human Mutation 30: 283-92 (2009).


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A. Veltman. Copy number variation. EUROGENE portal. September 2010. online:

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