Female carriers of an X-linked recessive mutation may manifest features of the disorder. Which of the following is the most common cause?
If a female is a carrier of an X-linked recessive condition one would expect her not to have features of the disease. With lyonization however an X chromosome in each cell is randomly deactivated. As the process is random the inactivation may be of the unaffected or affected X chromosome. In case where there are approximately 80% or more affected alleles the woman may show signs of the disease.
Heterodisomy20%Selection for the mutant allele19%Skewed X-inactivation18%Dominant negative mutation21%Maternal uniparental disomy22%
If a female is a carrier of an X-linked recessive condition one would expect her not to have features of the disease. With lyonization however an X chromosome in each cell is randomly deactivated. As the process is random the inactivation may be of the unaffected or affected X chromosome. In case where there are approximately 80% or more affected alleles the woman may show signs of the disease.
Lyonization
The X chromosome contains over 1,000 genes that are essential for proper development and cell viability. Females carry two copies of the X chromosome, resulting in a potentially toxic double dose of X-linked genes. To correct this imbalance, by way of the process called Lyonization (X-inactivation), females transcriptionally silence one of their two Xs. The inactivated X chromosome, then condenses into a compact structure called a Barr body, which is maintained in a silent state.
The process of X-inactivation is random. There is no preference for the inactivation of paternal or maternal X chromosomes. It occurs very early in embryogenesis, soon after the fertilization of the egg by the sperm (when the dividing conceptus is about 16-32 cells big).
It occurs in every female cell. X inactivation affects most but not all genes on the X chromosome. If a cell has more than two X chromosomes then the extra Xs are also inactivated.
