humans is mostly caused by secondary events rather than a genetic tendency. There is a much higher concordance rate in genetically identical (monozygotic) twins compared to non-identical (dizygotic) twins, which suggests a strong genetic input. A 10% difference in the skewing of genetically identical twins did exist however, so there are other contributing factors outside of genetics alone. It is difficult to identify primary nonrandom inactivation in humans, as early cell selection occurs in the embryo. Mutation and imprinting of the XIST gene, a part of the X-inactivation centre, can result in skewing. This is rare in humans. Xce Skewed X-inactivation in mice is controlled by the Xce gene on the X chromosome. Xce acts in cis, which means that it acts upon the chromosome from which it was transcribed. There are four alleles of Xce, labeled a, b, c, and d. Each allele has a different likelihood of inactivation, with a < b < c < d, where d is the most likely to remain active and a is the least likely. The strength differences between the four alleles are likely due to variations in the number of binding sites for a crucial actor in inactivation. The specific transfactor is not known currently. Homozygotic mouse cells will have roughly even levels of inactivation due to both alleles having equal chance of being inactivated. For example, a mouse with the genotype dd will have an inactivation ratio very close to 50:50. Heterozygotes, will experience greater levels of skewing due to the differing inactivation likelihood of the two alleles. A mouse cell with the Xce genotype ad will have a greater number of the a-carrying than d-carrying X chromosomes inactivated, because the d-carrying X chromosome is less likely to be inactivated. There are two theories on the mechanism Xce uses to affect inactivation. The first is that genomic differences in the Xce alleles alter the sequence of the long non-coding RNA that is an integral part of X chromosome inactivation. The second is that Xce acts as a binding site for dosage factors that will affect XIST gene and Tsix expression (long non-coding RNAs involved in X chromosome inactivation). Parent-of-origin Skewing can also be influenced by the parent-of-origin effect, in which skewing becomes biased towards either the maternal or paternal X chromosome. Studies have suggested an X-linked gene or genes that control this effect, but the exact gene has not yet