During the early embryonic development in women, a process known as X chromosome inactivation occurs, which causes random gene silencing of one of the two X chromosomes. In the case of random inactivation of the mother’s or the father's chromosome X, the ratio of active to inactive chromosome X is 1:1. Deviation from this ratio can be defined as a criterion for the non-random X chromosome inactivation (skewed X-inactivation). Several genes on chromosome X have been shown to have an effect on an individual's mental development, therefore mutations in those genes are often associated with development of mental disorders. The aim of this master's thesis was to introduce and validate a methodology for the X chromosome inactivation based on the use of polymerase chain reaction in combination with methylation-sensitive restrictases. With this method we then tested the pattern of X chromosome inactivation (random/non-random) in girls with intellectual disabilities compared to a control group of girls from the general population (healthy girls without intellectual disabilities). By calculating the coefficient of X chromosome inactivation and further processing the results, we demonstrated a statistically significant difference in occurrence of non-random X chromosome inactivation (p = 0.028) between the control group and the group of girls with intellectual disabilities. The obtained results enabled us a successful implementation of the methodology for determination of the X chromosome inactivation in the routine diagnostic process of the Laboratory of Medical Genetics in the University Medical Centre Maribor.
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