Team Decodes Down Syndrome Chromosome
The international Human Genome Project reported Monday that it has decoded the human chromosome responsible for Down syndrome, the most common genetic cause of mental retardation.
The “essentially finished” genetic code of chromosome 21, published in the journal Nature, is viewed as an important step by genetics researchers because of the new insights it offers into a disorder that strikes indiscriminately every racial and ethnic group in the world.
In the United States alone, more than 350,000 individuals have Down syndrome. One child is born with the condition in every 700 to 1,000 births.
These individuals often suffer from a variety of medical problems in addition to retardation, including heart defects, blockages in the digestive tract, and lung infections. They also have a high incidence of leukemia.
Most people with Down syndrome have an extra copy of chromosome 21 in every cell in their bodies, and identifying all the genes carried on that chromosome will help scientists understand the disorder and its many variations.
“We will not have a gene therapy tomorrow as the result of finding the sequence today,” said Roger H. Reeves, a geneticist at Johns Hopkins University School of Medicine. “But it will allow the research community to greatly focus on a small set of genes as the primary cause of what goes wrong in Down syndrome.”
This is the second chromosome that the publicly funded Human Genome Project has deciphered so far, and it is the smallest of all the human chromosomes.
Deciphering or sequencing a chromosome means determining the order of millions of chemical building blocks in DNA, the molecule that carries the genetic code. The information will help scientists discover the number, placement and function of genes--long stretches of DNA that most often contain the directions for manufacturing one or more proteins needed for growth and maintenance of health.
Scientists believe that cracking the genetic code will lead to new treatments and methods of diagnosis for many human ills, including cancer and heart disease and perhaps the effects of aging itself.
The 16 centers in the international public consortium announced separately that they have all but completed their “working draft” of the human genetic code and are beginning to fill in the missing pieces to produce a more finished version of all the human chromosomes by 2003.
The first draft, expected to be available on a public Web site in June, will include 90% of the code from a reference set of 24 chromosomes--Nos. 1 through 22 plus the X and Y chromosomes that determine gender--drawn from 10 anonymous donors.
The announcements come amid growing expectations that a biotech company, Celera Genomics, will announce its draft of the genome--the entire genetic code of an anonymous individual--in the next several days.
The tension of competition is running particularly high this week, near the start of the most important annual genome conference, which begins Wednesday at the Cold Spring Harbor Laboratory, a major research and meeting center on Long Island, N.Y.
Researchers with the public project admit that the timing of the announcements is not a coincidence. The findings in the chromosome 21 paper will appear in the May 18 edition of Nature, but an electronic version was released Monday, after news conferences by researchers at genome centers in Japan and Germany who released the results.
Most startling in the chromosome 21 findings is the relatively small number of genes found on the chromosome--far fewer than the amount of DNA present would indicate. The Human Genome Project scientists estimate that there are a total of 225 genes on chromosome 21, compared with 545 on chromosome 22, the only other chromosome to have reached this stage of completion.
Based on those results, the researchers now say there may be only 40,000 human genes--far less than the 100,000 usually estimated. That opens up whole new questions about how genes operate.
Large chunks of both chromosomes 21 and 22 remain incomplete because some sections of DNA are impossible to sequence using current technology, which is why they are considered “essentially finished” rather than totally complete. But the areas that are sequenced contain almost all the genes.
The findings on chromosome 21 provide a solid basis for understanding Down syndrome and other conditions, said Dr. Julie Korenberg of Cedars-Sinai Medical Center in Los Angeles and a professor of pediatrics and human genetics at UCLA.
“It’s not an accident that the two smallest chromosomes were the first sequenced,” she said. Because the two are so different, they give scientists a view of how genes are organized into varying regions. “Chromosomes are not just strings of genes,” she said.
For those with Down syndrome and their families, the growing knowledge about the relatively small number of genes on chromosome 21 offers cause for hope--opening up a world of possible intervention to boost intelligence and prevent disease even after birth.
“How many IQ points would it take to give large numbers of children with Down syndrome the ability to function in normal society? Not many,” Korenberg said. “We may be able to improve function in specific areas by understanding one or a few genes.”
