Staking Out Our Sexual Legacy

Biologists have completed their best physical map yet of the X chromosome, one of the two chromosomes (the other is the Y) that determine whether we are male or female. The achievement, reported in the March issue of Genome Research, moves genome scientists a big step closer to sequencing the X chromosome and should speed their hunt for genes involved in everything from sexual maturation to mental retardation.

In an effort equivalent to planting road markers along an interstate highway, molecular biologist David Schlessinger, of Washington University in St. Louis, and colleagues sequenced some 2100 short stretches of DNA spaced roughly equally along the X chromosome's 160 million base pairs. This gives Schlessinger's map three times as many markers as the previous chromosome X map. Its density (one marker for every 75,000 base pairs) exceeds the minimum threshold for staking out a chromosome--as set by the Human Genome Project, which has decreed that geneticists need these signposts every 100,000 base pairs. Having longer stretches of DNA between markers would make it too difficult for molecular biologists to keep track of their location along a chromosome as they sequence its DNA.

The new map reveals some surprises. It points to a "cold" spot, a stretch of 20 million base pairs where recombination--a process in which genes are swapped between two copies of the same chromosome during formation of the egg and sperm--does not occur. "No one anticipated that," says Schlessinger. Scientists had thought the likelihood of two genes undergoing recombination was determined solely by the distance between them. This finding suggests that the sequence of base pairs in a chromosome could also affect the rate of recombination. The cold stretch lies along part of the chromosome implicated in premature ovarian failure syndrome, in which women undergo early menopause. However, it is unclear how the lack of recombination could play a role in the syndrome.

Even with this level of detail, more genetic road markers should be planted before geneticists gear up for a nucleotide-by-nucleotide sequencing offensive. Nevertheless, chromosome X "is one of the first chromosomes seriously out of the gate" for sequencing, says Eric Green of the National Human Genome Research Institute in Bethesda, Maryland. He has completed a similar map of chromosome 7. With the current rate of progress, Green predicts the X chromosome will be sequenced by the year 2000.

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