Please cite this paper as: Choy K, Setlur S, Lee C, Lau T. The impact of human copy number variation on a new era of genetic testing. BJOG 2010;117:391–397.
Cytogenetic studies have demonstrated that duplications or deletions of entire chromosomes or microscopically visible aberrations are associated with specific congenital disorders. The subsequent development and application of microarray-based assays have established the importance of copy number variants (CNV) as a substantial source of genetic diversity in the human genome. Pathogenic CNVs are associated not only with birth defects and cancers, but also with neurodevelopmental disorders at birth or neurodegenerative diseases in adulthood. Unfortunately, the limited knowledge of the phenotypic effects of most CNVs has led to the classification of many CNVs as genomic imbalances of unknown clinical significance. This has caused many clinicians to resist the introduction of microarray technologies in detecting CNVs in a genome-wide manner for prenatal applications. This review summarises our current understanding of CNVs, the common detection methods, and the implications for human health and prenatal diagnosis.