The reason females are less often affected by recessive alleles is not as simple as it is for autosomes. Since females have twice the number of X chromosomes as males, the question arises as to whether they make twice the amount of each X-encoded protein as males do. In fact they do not, and are prevented from doing so by the random inactivation of one X chromosome in each cell. Therefore, about half of the heterozygote female's cells will express the normal allele, and half will express the harmful recessive allele. This is in contrast to the situation for autosomes, in which each cell expresses both alleles.
Inactivation begins early in development, with some cells shutting down one X and others shutting down the other, followed by faithful inheritance of the inactivated chromosome by each daughter cell following cell division. As a result, many tissues in the adult female are a mosaic of cells with different X chromosomes inactivated. The consequence of this is seen in a woman who is heterozygous for a harmful allele. If the affected tissue is primarily composed of cells expressing only the harmful one, she is likely to express the trait. However, most adult tissues will be a more even mixture, and for many disorders this will prevent her from developing symptoms of the disease.
The trait may also show variable expressivity, with the severity dependent on the proportion of the tissue affected. Duchenne muscular dystrophy in females is an example. Many women with one disease allele will show no symptoms. Others will develop only slightly elevated blood levels of cer-
ftain enzymes indicating mild muscle damage, while others will develop heart problems and muscle weakness. Such women are referred to as "manifesting carriers."
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