X-chromosome tells the tale

March 16, 2005

HOUSTON - (March 17, 2005) - If the human genome is indeed the "book of life," then the X-chromosome is all plot.

In a report in today's issue of the journal Nature, a host of genome researchers describe the nature of this mysterious "chapter" in the DNA story.

"Large numbers of medically related genes happen to fall on the X," said Dr. Steven Scherer, associate professor in the Baylor College of Medicine department of molecular and human genetics and director of mapping in the BCM Human Genome Sequencing Center. "For a chromosome that is so bereft of genes compared to other chromosomes, this one is well characterized with regard to disease genes."

The fact that men have just one copy of the X chromosome makes the mutated genes on that one piece of DNA much easier to find, said Scherer.

Scherer and his colleagues in the BCM Sequencing Center were the number two contributors to the sequencing effort directed at the X chromosome. It was led by the Wellcome Trust Sanger Institute in Britain.

The story of each chromosome will be published eventually, with all the important features explained, said Scherer.

"I expect this chromosome is the all-star of the series. It will make interesting reading for the general scientific population and the lay public," he said. "If you were going to read a chromosome paper, this probably ought to be the one you read."

The role of the X and Y chromosomes have evolved. Before the split between birds and mammals, the X and Y chromosomes were just like any other pair of chromosomes - each was fairly similar and carried similar information.

The authors, in tracing the evolution of the X chromosome, showed that slowly, but surely, the Y chromosome "dropped off the face of the earth," said Scherer. "Although it contains a few important genes, it's almost like the appendix of the human genome."

Every woman has two X chromosomes. Each man has an X chromosome and a Y chromosome. In women, one of the X chromosomes is largely inactivated. Because there are actually few genes on the Y chromosome, inactivating most of one of the X chromosomes in women means that men and women each have one active X chromosome, where most of the coding information exists.

Among the most important actions of the Y chromosome is the determination of sex. In fact, the paper indicates that 10 percent of genes that cause production of proteins on the X produce genes most often expressed in the testis but that have increased activity in tumors of the testicles, melanoma and other cancers.

Over the past few years, the BCM sequencing center and others around the world have concentrated on sequencing the genomes of organisms studied in the laboratory. The future will look more closely at the human genome and its variations, said Scherer.

"The National Human Genome Research Institute is moving into a comprehensive program defining variations of all the genes in the genome," he said. That means looking at both normal subjects and patients with diseases.

"Papers like this one define the starting gate," said Scherer. "Now the research community is taking the next step. We are in a unique position at BCM of being in the largest clinical concentration in the world. We have more samples and examples of human disease right on our doorstep than most other centers. We mean to take that information, leverage and run with it. We hope this community will be the first to benefit from these kinds of advances."

Baylor College of Medicine

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