Structural variation in the human genome: the impact of copy number variants on clinical diagnosis

Abstract

Over the past few years, the application of whole-genome scanning array technologies has catalyzed the appreciation of a new form of submicroscopic genomic imbalances, referred to as copy number variants. Copy number variants contribute substantially to genetic diversity and result from gains and losses of genomic regions that are 1000 base pairs in size or larger, sometimes encompassing millions of bases of contiguous DNA sequences. As genome-wide scanning techniques become more widely used in diagnostic laboratories, a major challenge is how to accurately interpret which submicroscopic genomic imbalances are pathogenic in nature and which are benign. Herein, we review the literature from the past 3 years on this new source of genomic variability and comment on factors that should be considered when trying to differentiate between a pathogenic and a benign copy number variant.