and find single nucleotide polymorphisms (SNP) that are associated with the disease. These SNPs are genotyped and traced to parental contributor to calculate the ratio of inactivation, based on how much genetic information each parent donated and how much of each parental allele is expressed. These levels of expression may give greater insight to the fundamental cause of the diseases seen from skewed X-inactivation. Potential problems There are several factors which must be taken into account when studying skewed X-inactivation. Escaped genes are ones found on the inactive X chromosome but are still expressed; this particular gene will be expressed from both chromosomes. It is estimated that 25% of the genes escape inactivation. Genes used to study skewing must be carefully selected to ensure they do not escape inactivation, as they will not show any skewed pattern. A skewed pattern might be more common in affected females than unaffected. This must be considered when studying X-linked diseases. Due to the random nature of inactivation, women can have skewed inactivation due to simple statistical probability. This makes it difficult to determine when the ratio is abnormally skewed. Additionally, skewed activation can also be localized to specific cell lineages. For example, one woman might have skewed activation in her T cells but not the B cells, which in turn necessitates deep analysis work and adequate control of cell lines to ensure proper diagnosis. References Epigenetics