Investigating X-Chromosome Inactivation

Females have two alleles for each gene on the X- chromosome, whereas males have only one. This inequality is balanced by X-chromosome inactivation (XCI). This process transcriptionally silences one X- chromosome in every female cell. The choice of which X-chromosome should be “turned-off” is considered to be random. Studies on mice have revealed that a locus on the X-chromosome, the X controlling element (Xce), significantly influences the choice of which X- chromosome is inactivated. Renault et al. (2007) studied a family of which many of the females exhibit symptoms of the X-linked recessive disease, Haemophilia A. The XCI ratios of the women in this family were significantly different from what would be expected if the XCI process was random. This studies result is consistent with the human XCE hypothesis. Random and genetic models of XCI ratios are investigated here in theory and are compared to a sample of XCI ratios. Using goodness-of- fit testing, it is determined which models best fit the data. Anderson-Darling statistics and visual inspection of graphics suggest that a three allele genetic model is a good fit to the data, supporting the human XCE hypothesis.