National Foundation for Ectodermal Dysplasias

Lyonization
Lyonization is the term which describes the process by which human beings level their genetic playing field.
Human males and females have 46 chromosomes in 23 pairs. Males and females share in common the first 22
pairs of chromosomes, but differ in the pair known as the sex chromosomes. Females have two X chromosomes;
males have one X chromosome and one Y chromosome.
The X chromosome is loaded with genetic information. The Y chromosome carries very little except factors that
help determine maleness. In order to compensate for the double dose of genes on the X chromosome in
females, an event occurs very early in the embryogenesis of a 46, XX conception, soon after the fertilization of
the egg by the sperm. At this stage, when the dividing conceptus about 16-32 cells big, in each cell one of the
two X chromosomes turns off. It stops producing information. This is referred to as X-inactivation, or lyonization
(the term lyonization is in honor of Mary Lyon, the scientist who first offered this explanation for gene dosage
compensation). This inactivation process does not occur in males because they have only one X chromosome.
This process is most often random. The specific X turns off in each cell is an act of chance and it is permanent.
The same X chromosome will remain inactive in all the daughter cells which develop from then on. Thus, every
female has some cells in which her mothers X is active, and some in which her fathers X is active. Most of the
time, it turns out to be about 50-50, by chance alone. Sometimes a greater percentage of cells will have one or
the other X active.
When a genetic condition is caused by a gene that is carried on the X chromosome, males will show it because it
is only the gene they have, having only one X chromosome. Females may not show it at all, may show the
condition to some degree, or may have as many problems as an affected male. This is all dependent upon Xinactivation. If most cells in a female carrier have the X with the normal gene active, the girl will have no signs of
the disorder. If most of the cells have the X with the altered gene active, then the child will have as many
problems as a male with the condition.
Females with X-linked hypohidrotic ectodermal dysplasia show this pattern. Some carriers have almost no
detectable changes, most have a few altered teeth or patchy hair or mild heat intolerance, and some have all the
features that are seen in their affected male relatives.
When it comes to the risk for a carrier female of an X-linked condition to have affected children, lyonization
makes no difference. In the ovaries, each X reactivates and each egg has an equal likelihood of carrying the X
with the gene for the condition or the X with the normal gene. This is true whether the woman has no features
of the disorder, or is severely affected.
All mammals compensate for the male-female chromosome difference in this way. I bet you would like to know
how fruit flies do it!
Virginia P. Sybert, M.D.
University of Washington
Group Health Permenente
Update 04

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