The Velocardiofacial syndrome is characterised by a complex clinical behavioural phenotype, resulting from the imbalance of normal dosage genes located on 22q11. Low copy repeat gene clusters are known to flank the microdeleted region and predispose to unequal crossing over events resulting in the interstitial 22q11 deletion. Involvement of multiple disease genes is strongly suspected and traditional positional cloning techniques as well as mouse models are used to identify the involved genes.