A complex interplay of molecular factors is likely to be responsible for the trisomic phenotypes, possibly involving non-chromosome 21 genes. Furthermore, interaction of trisomy with the presence of certain embedded deleterious alleles or haplotypes may contribute to the variable presentation of the different phenotypes (including degree of mental retardation, congenital heart defects, Hirschprung and other gut diseases, and leukaemia). The increasing amount of copy number variation that has been discovered in the human genome, specifically on chromosome 21, adds another dimension to the molecular consequences of trisomy: it is possible that the phenotypic variability seen in DS may be due to CNVs on this chromosome.