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Researchers Analyze X Chromosome Genes

March 16, 2005

Women get more work out of hundreds of genes on the X chromosome than men do, and that could help explain biological differences between the sexes, a new study says. The results imply that women make higher doses of certain proteins than men do, which could play out in gender differences in both normal life and disease, researchers said.

So far, however, none of the genes identified in the study has been linked to any such observable differences, said senior study author Huntington Willard of Duke University.

He and Laura Carrel of Pennsylvania State University describe their analysis of the X chromosome genes in Thursday’s issue of the journal Nature.

A second paper in the same issue presents a comprehensive analysis of the chromosome’s DNA, in which an international team of scientists found 1,098 genes.

Chromosomes are the threadlike packages of genes and other DNA found in cells of the body. People have 24 kinds, numbered 1 through 22 plus the X chromosome and its runty partner, the Y. Women carry two copies of the X chromosome, one inherited from each parent, while men have one X plus one Y chromosome.

Long before birth, females permanently turn off one copy of their X chromosome in each cell, so that like males they operate with just one copy functioning. But scientists have long known that inactivation isn’t perfect. Some genes on the inactivated copy continue to function, sending out chemical orders for the cell to manufacture specific proteins.

The work by Willard and Carrel suggests the inactivated chromosome contains 200 to 300 such genes, in two categories.

First, they found that 15 percent of the inactivated chromosome’s genes continue to function to some degree. More surprising, Willard said, was what researchers discovered about another 10 percent of the genes. For each, the activity level varied widely from one woman to the next, from zero in some women to varying levels in others.

That contrasts with the relatively consistent activity levels one sees in X chromosomes from men, or in other chromosomes in either sex, Willard said.

In fact, when the study compared the inactivated X chromosomes of 40 women, each of them showed a different pattern of gene activity, Willard said.

Dr. Jeannie T. Lee, who studies X chromosome inactivation at Harvard Medical School, said the study provides a better estimate than scientists had before of how many genes escape inactivation. And she agreed that the variability between women was a surprise.

The work raises the possibility that varying activity of genes on the X chromosome can account for not only some differences between the sexes, but also between women, she said.

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