Methods and strategies for analyzing copy number variation using DNA microarrays

Abstract

The association of DNA copy-number variation (CNV) with specific gene function and human disease has been long known, but the wide scope and prevalence of this form of variation has only recently been fully appreciated. The latest studies using microarray technology have demonstrated that as much as 12% of the human genome and thousands of genes are variable in copy number, and this diversity is likely to be responsible for a significant proportion of normal phenotypic variation. Current challenges involve developing methods not only for detecting and cataloging CNVs in human populations at increasingly higher resolution but also for determining the association of CNVs with biological function, recent human evolution, and common and complex human disease.

Figure 1

Array-CGH profiles of a small region of chromosome 18 for two normal DNAs. Copy-number ratio is graphed on the y axis. (a) High-resolution NimbleGen oligonucleotide array. The red horizontal lines indicate regions of similar copy number. Numbers 1 and 2 indicate clusters of probes (CNVs) with low and high ratios, respectively. (b,c) Replicate whole-genome large-insert clone tiling path array hybridizations. Clones called as identifying CNVs are indicated by the red horizontal lines and other clones by black horizontal lines; the lengths represent the sizes of the clone inserts. Modified from a display generated in SignalMap (NimbleGen Systems).