On the DGV, there are 507 reported CNV calls covering 35.0% of chromosome 21, which is similar to the CNV coverage of other chromosomes (33.9%) (DGV March 2010). Many of these are common in the population. For example, our investigation of only 50 healthy French male samples revealed 20 multi-probe CNVs, and an additional 57 single probe CNV signals, on chromosome 21 (de Smith et al. 2007 ): almost half were detected in multiple samples (47%), and 34% had a frequency of [5% (Fig. 2 ). In addition, these CNVs overlapped 38 known genes. There were several CNVs within TIAM1 (T-lymphoma invasion and metastasis-inducing protein 1), for example, which is expressed in almost all analysed tumour cell lines, including B-and T-lymphomas, melanomas and carcinomas (Habets et al. 1995) . A CNV was also found within DSCAM¸which is a good candidate gene for the CHD phenotype seen in DS, as it lies within the predicted minimum critical region and is expressed in the heart during cardiac development (Korbel et al. 2009 ). Several other CNVs have since been discovered in this gene, as listed on the DGV, including a common deletion that incorporates 4 exons (Matsuzaki et al. 2009 ).