CNVs also overlap RUNX1, with one deletion removing the promoter region and first exon of this gene (Gusev et al. 2009 ). RUNX1 codes for a transcription factor involved in haematopoiesis (North et al. 2002) and is associated with AMKL, which is estimated to be 500-fold more frequent in children with DS than in the general population (reviewed in Zipursky et al. 1992) : CNVs in this gene may, therefore, protect against or increase susceptibility to leukaemia in DS. These CNV loci and other regions that could potentially impact variable phenotypes of trisomy 21 are listed in Table 3 .