Scientists map human chromosome associated with Down syndrome

In an achievement that could point the way to treatments for a host of illnesses, scientists have mapped chromosome 21, the smallest human chromosome and the one associated with Down syndrome, epilepsy, Lou Gehrig's disease and Alzheimer's.

It is the second human chromosome whose DNA has been fully deciphered. Chromosome 22 was mapped last fall.

''Another volume has just been placed on the shelf. Now we really have to roll up our sleeves and assess what these genes are doing there, what role they play in causing disease,'' said Francis Collins, chairman of the Human Genome Project at the National Institutes of Health in Bethesda, Md.

The German- and Japanese-led team that mapped chromosome 21 is part of the Human Genome Project, an international effort to decipher chemically the entire human genetic blueprint.

On Monday the project also announced that it is moving into the final phase of cataloging the human genes. Having collected about 90 percent of the estimated 3 billion letters in the DNA code, the project is moving on to a final ''finishing'' phase in which it will attack the difficult sections that remain and proofread what has already been acquired.

''We have made a really important transition and we're very excited about it,'' said Eric Lander, director of the Whitehead Institute Center for Genomic Research, one of 16 laboratories involved in the Human Genome Project.

Chromosome 21 contains relatively few genes, but they are in a complex tangle. Humans are normally born with 23 different pairs of chromosomes, which are made up of genes.

''When one stares at a sequence like this, it makes you realize how complex it really is,'' said Huntington F. Willard, chairman of genetics at Case Western Reserve University. He was not involved in the research.

''It's not just a simple string of 225 genes. It's really a mess, a hornet's nest - a hodgepodge of duplications, altered sequences and arrangements that determine the health and welfare of our species.''

The findings will be published in Thursday's issue of the journal Nature.

The researchers found that chromosome 21 contains far fewer genes than the 545 in chromosome 22, the second-smallest chromosome.

The relative sparseness of genes in chromosome 21 may mean the total number of genes in human DNA is under 40,000 - not the 100,000 or more that had previously been thought, said Andre Rosenthal, a professor at the Institute for Molecular Biotechnology in Jena, Germany.

That means ''we are not so different from drosophila'' - the fruit fly - ''or yeast,'' Rosenthal said.

The map of chromosome 21 is 99.7 percent complete; technical limitations prevented a complete mapping, said David Patterson, an American scientist involved in the project.

Patterson said the map may allow researchers to home in on specific genes in the chromosome that cause mental retardation in people with Down syndrome and then perhaps develop drugs to treat such patients.

''Once we can find the genes that are important for learning problems, what we hope is that we'll be able to understand what those genes do and somehow compensate for having an extra copy of the gene,'' said Patterson, president of the Eleanor Roosevelt Institute in Denver and chairman of the science advisory board of the National Down Syndrome Society.

Down syndrome occurs when a person is born with an extra, third copy of chromosome 21. Down syndrome, the most common form of genetically caused mental retardation, occurs in about one in 700 live births. Down syndrome can also cause congenital heart disease and Alzheimer's by age 40.

Rudolph Tanzi, a professor of neurology at Harvard Medical School, said the chromosome map could eventually shed light on why people with Down syndrome have a very low rate of breast, lung and gastrointestinal cancers. It could be that an extra copy of chromosome 21 has tumor-suppressing qualities.

''One can argue that an extra dose of a gene will usually be a bad thing, but once in awhile it can be a good thing. It can be protective,'' Tanzi said.

The Human Genome Project expects to have a rough draft of the entire human genetic blueprint done this summer. The public project, which is expected finish its work by 2003, is competing against a private company, Celera Genomics Corp. of Rockville, Md., which hopes to sell the information to pharmaceutical companies and others.


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