In polyploidy or sub-chromosomal duplications where abnormalities result from extra copies of the chromosome regions, deletion CNVs may ''normalise'' copy number. Alternatively, there is potential for even greater amplification of copy number where amplification CNVs are present. A simple duplication CNV on the non-disjoining chromosome may lead to the presence of up to six copies of a gene in a trisomic individual (Fig. 1 ) and the subsequent phenotypic effects associated with increased gene expression levels. Conversely, a gene deletion on the non-disjoining chromosome may alleviate the expected effect of trisomy by reducing the local copy number state to one or two copies. Thus, the compounded effect of aneuploidy and copy number variation has the potential to generate a much wider range of phenotypes than would be expected on the basis of chromosome number alone. It has been suggested, therefore, that CNVs are likely to act as 'modifiers of the phenotypic variability of trisomies' (Beckmann et al. 2007 ) and the same is probably also true for smaller chromosomal imbalances.