On March 14, researchers at Washington University School of Medicine in St.Louis announced the completion of a high-resolution map of chromosome X. This chromosome, which determines gender, is associated with many inherited disorders. Researchers also located hot spots for genes and detected a large region where the DNA remains intact as it passes from one generation to another.

Published in the March issue of Genome Research, the map has 2100 unique landmarks --three times as many as any previous X chromosome map. If it were a road map from St.Louis to San Francisco, it would show a marker every mile. On average, the new map has a landmark every 75,000bp. The national goal for chromosome mapping is one landmark every 100,000 bp.

David Schlessinger, director of the Center for Genetics in Medicine and principal investigator for the NIH-funded X project, said, "Completion of a map with this level of detail has made X one of the earliest chromosomes for DNA sequencing'the next phase of the Human Genome Project."

X chromosome's completion has permitted a refined comparison between a physical map and a genetic map, which is constructed by studying the passage of traits from one generation to another. When researchers compared the X genetic map, with its few hundred markers, to the physical map, they found an area in the middle that corresponds with a much longer stretch (17Mb) of the physical map. "So this region is uneventful on the genetic map, whereas it contains a whole bunch of markers on the physical map," Schlessinger said. "But we don't know why the X chromosome should have this large area of poor recombination." He speculates that the answer may involve the X-inactivation locus, which in women turns off most of the genes on one copy of X, leaving the other to direct biological activities. The region of low recombination is on X's long arm, beginning near the X-inactivation locus and ending at a distinctive region that also is seen on the Ychromosome.

As YACs containing the relevant regions of X became available, Schlessinger and colleagues located genes for several diseases. These included an overgrowth disorder called Simpson-Golabi-Behmel syndrome and ectodermal dysplasia, which impairs the development of hair follicles, teeth, and sweat glands.