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Variation in women's X chromosomes may explain differences among individuals, between sexes

inactivation.

Originally, scientists had assumed that the inactivation process resulted in complete silencing of the genes on the second X chromosome, Willard said, in order to leave both sexes with the same activity level, or dosage, of the genes encoded by the X chromosome. Scientists had also implicitly assumed that the X chromosomes in all women would be identical.

Earlier work of Willard and others shattered the first assumption, when, in the late 1980s, the first evidence came to light that some portion of the genes on the second X chromosome in women remained active.

The new work extends that earlier finding to the full set of X-linked genes and also further reveals that individual women exhibit extensive differences among them with respect to X inactivation, Willard said.

In their study, the researchers isolated cell lines from each of 40 women. They then measured the activity level of each of 471 genes to determine whether the second copy was turned on or off.

Overall, about 15 percent of genes on the second X chromosome escape inactivation to some degree, they found. The proportion of genes that remain active differs dramatically among regions of the X chromosome, they reported.

Furthermore, in some women but not others, an additional 10 percent of X-linked genes demonstrate variable patterns of inactivation and different levels of activity in the "silenced" X chromosomes, the team reported.

"The findings suggest a remarkable and previously unsuspected degree of expression heterogeneity among females in the population," Willard said. Further work is required to explore potential consequences of that variation, he added.

However, the large number of genes that escape inactivation and their concentration in certain portions of the X chromosome has immediate implications for counseling the one in every 650 individuals born with X chromosome abnormalities, Willard said. The expected severity of
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-660-1306
Duke University Medical Center
16-Mar-2005


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