X inactivation

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Posted 12-10-99

Researchers study gene inactivation on X chromosome

Genetic abnormalities on short arm may have larger health consequences than abnormalities on long arm

In mammals, most of the several thousand genes located on one of a female's two X chromosomes are silenced through a mechanism known as X inactivation, which likely evolved to equalize the impact of X-linked genes in males and females. Genes that escape X inactivation may affect males and females differently. Such "escapees" have been thought to be quite rare.

However, in the December 7 issue of the Proceedings of the National Academy of Science, an article by researchers in the Department of Genetics at Case Western Reserve University's School of Medicine and from the University Hospitals of Cleveland Research Institute reported that 34 of 224 human X-linked genes escape inactivation.

The researchers found that distribution of escapees on the "arms" of an inactivated X chromosome is not random, with 30 percent of the genes on the short arm escaping inactivation, compared to only 3 percent of the genes on the long arm.

This distribution suggests that the two arms of the X chromosome may have different evolutionary origins, and that genetic aberrations which produce multiple copies of the short arm may cause more-significant health problems than those caused by aberrations producing multiple copies of the long arm.

Both the large number of genes that escape inactivation and their non-random distribution have implications for counseling individuals who have structurally abnormal X chromosomes. The initial X-inactivation profile presented in the paper represents an estimated 10 percent of all X-linked genes.

As the Human Genome Project progresses, a more complete picture of X-inactivation will emerge, shedding light on the organization of genetic material on the X chromosome.

All of the paper's authors are in the genetics department at CWRU. They are Laura Carrel; Amy Cottle; Karrie C. Goglin; and Huntington Willard, who is the department chair and director of the UHC Research Institute. Their work was supported by the National Institutes of Health.

-CWRU-