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Studies expand understanding of X chromosome

is confirmed the existence of 1,098 protein-coding genes on the X chromosome. Only 54 of the 1,098 genes have functional counterparts on the much smaller Y chromosome, which has been described as an "eroded" version of the X chromosome. Interestingly, almost 10 percent of the genes on the X chromosome are part of a somewhat mysterious family of "cancer-testis antigens," which are normally expressed in the testis but also appear in certain cancers, making them possible targets for immunotherapy.

The X chromosome's gene density is among the lowest for the human chromosomes that have been analyzed to date. Researchers say this may reflect a low density of genes on the ancestral chromosome that gave rise to the X chromosome, or it may indicate that genes coding for key proteins that are required in double dose were transferred from the X chromosome to other chromosomes during the course of mammalian evolution.

Despite its relatively low gene density, the X chromosome holds a prominent place in the study and understanding of human disease. This arises from the fact that any defects in genes on the X chromosome are often apparent in males because the Y does not carry corresponding genes to compensate. More than 300 diseases already have been mapped to the X chromosome, and though the X chromosome contains only 4 percent of all human genes, it accounts for almost 10 percent of inherited diseases caused by a single gene, which doctors often refer to as Mendelian disorders. These "X-linked" disorders include red-green color blindness, hemophilia, varied forms of mental retardation and Duchenne muscular dystrophy.

"From studying such genes, we can get remarkable insight into disease processes. But the importance of the sequence goes beyond individual genes. We have also gained a deep insight into the way evolution has shaped the chromosomes that determine our gender to give them unique properties," said Mark Ross, Ph.D., project leader at the Wellcome
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Contact: Geoff Spencer
spencerg@mail.nih.gov
301-451-8325
NIH/National Human Genome Research Institute
16-Mar-2005


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