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The clinical context of copy number variation in the human genome

Published online by Cambridge University Press:  09 March 2010

Charles Lee  and
Stephen W. Scherer
Charles Lee
Affiliation:
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Stephen W. Scherer*
Affiliation:
The Centre for Applied Genomics and Program in Genetics & Genome Biology, Hospital for Sick Children, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
*
*Corresponding author: Stephen W. Scherer, The Hospital for Sick Children, MaRS Centre - East Tower, 101 College Street, Room 14-701, Toronto, Ontario, M5G 1L7, Canada. E-mail: stephen.scherer@sickkids.ca
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Abstract

During the past five years, copy number variation (CNV) has emerged as a highly prevalent form of genomic variation, bridging the interval between long-recognised microscopic chromosomal alterations and single-nucleotide changes. These genomic segmental differences among humans reflect the dynamic nature of genomes, and account for both normal variations among us and variations that predispose to conditions of medical consequence. Here, we place CNVs into their historical and medical contexts, focusing on how these variations can be recognised, documented, characterised and interpreted in clinical diagnostics. We also discuss how they can cause disease or influence adaptation to an environment. Various clinical exemplars are drawn out to illustrate salient characteristics and residual enigmas of CNVs, particularly the complexity of the data and information associated with CNVs relative to that of single-nucleotide variation. The potential is immense for CNVs to explain and predict disorders and traits that have long resisted understanding. However, creative solutions are needed to manage the sudden and overwhelming burden of expectation for laboratories and clinicians to assay and interpret these complex genomic variations as awareness permeates medical practice. Challenges remain for understanding the relationship between genomic changes and the phenotypes that might be predicted and prevented by such knowledge.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e8
Copyright
Copyright © Cambridge University Press 2010

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References

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Further reading, resources and contacts

The Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources

(DECIPHER) provides tools that allow researchers to share information about copy number changes in patients:

https://decipher.sanger.ac.uk/Google Scholar
http://projects.tcag.ca/variation/Google Scholar
http://www.ncbi.nlm.nih.gov/omim/Google Scholar