Dosage imbalances in haploid mammalian cells. (A) The inequality of parental genome contributions is illustrated by the Igf2-H19 imprinted gene cluster. In bi-parental diploid cells, H19 is expressed from the maternal whereas Igf2 is expressed from the paternal inherited chromosome. Haploid cells only contain a single set of chromosomes, either the maternal or paternal, and therefore lack either Igf2 or H19 expression. (B) The cell volume of haploid cells is between 50 to 66% that of diploid cells. This leads to changes in the surface area to volume ratio and the cell diameter that can influence transport processes and extension of the mitotic spindle, respectively. In addition, dosage compensation by X inactivation is not feasible in a haploid karyotype and, as a consequence, a genetic imbalance is incurred as the X chromosome to autosome (X/A) ratio is elevated to 1:1 from 1:2 in normal diploid cells. This effect is only significant after embryonic stem (ES) cell differentiation as normal diploid ES cells are not dosage compensated by X inactivation.