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Two human chromosomes entirely mapped.

In two of the earliest major advances in the mammoth international effort to identify and decipher all of the estimated 100,000 human genes, two groups of researchers have taken apart and put back together the smallest human chromosomes: the Y chromosome and chromosome 21.

The exercise have yielded for each chromosome a set of overlapping segments of DNA assembled in the correct order. Scientists expect both of these so-called physical maps to help them find new genes more quickly. They also predict that the map of the Y chromosome will shed new light on human evolution.

Scientists at the Whitehead Institute for Biomedical Research in Cambridge, Mass., constructed the physical map of the Y chromosome. The team, led by David C. Page, began by examining the Y chromosomes of individuals who had inherited only fragments of this rod-shaped structure, which bears the genes that make a male.

By comparing the different-size Y chromosome fragments of 96 such individuals, Page and his colleagues discovered naturally occurring breakpoints that they could use as molecular probes. This comparison also allowed the researchers to organize the probes into the order in which they would occur in an intact Y chromosome.

Page's group then used the probes to isolate long pieces of the Y chromosome from a man who had three extra Y chromosomes, which provided the researchers with an abundance of material for study. By assembling the pieces in the order of the probes, Page and his colleagues reconstructed 98 percent of the part of the Y chromosome that contains genes. They describe their work in two papers in the Oct. 2 SCIENCE.

Douglas Vollrath, a key member of Page's group, says the discovery should speed the Human Genome Project. "Until recently, the most difficult part was finding the DNA that you thought contained a particular gene," says Vollrath. "Now the problem can go to the freezer and pull out a vial that contains the DNA you want."

Simon Foote, another key group member, adds, "This map and future maps will serve as the substrate for large-scale sequencing efforts" to read every letter in the encyclopedia of DNA that makes up the human genetic complement.

Vollrath and Foote say they plan to use detailed maps of the Y chromosome to shed light on the male side of human evolution. Several teams of evolutionary biologists have already used sporadic mutations in mitochondrial DNA -- genetic material located outside the cell nucleus and inherited only from the mother -- in attempts to trace human origins.

A team of 36 researchers from Europe, the United States, and Japan collaborated on the physical map of chromosome 21. Led by Daniel Cohen of the Paris-based Center for the Study of Human Polymorphism, they discovered 198 equally spaced landmarks on chromosome 21. These landmarks allowed the researchers to divvy the chromosome up into manageable chunks and to assemble the chunks in the correct order, they report in the Oct. 1 NATURE. Chromosome 21 is particularly important to human disease, Cohen and his colleagues state, because it contains the genes for amyotrophic lateral sclerosis (Lou Gehrig's disease) and for some forms of Alzheimer's disease and epilepsy. An extra copy of chromosome 21 causes Down's syndrome.

The maps of the two chromosomes "represent a massive body of work," Peter Little of Imperial College in London comments in an editorial in the Oct. 1 NATURE. "The important message is that [such mapping] can be done and it is now only a matter of time (and money) before all human chromosomes are completed."
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Title Annotation:Y chromosome, chromosome 21
Author:Ezzell, Carol
Publication:Science News
Date:Oct 3, 1992
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