May 8, 2000 -- With their new genetic inventory of chromosome 21, scientists may have taken another big step toward understanding and treating genetic diseases. And with a map of this chromosome, the second such genetic compilation assembled since chromosome 22 was mapped last year, fellow investigators say they now have a solid foundation for their own studies.
"For Down's syndrome researchers, this is really a major milestone," physiologist Roger Reeves, PhD, tells WebMD. "So now we have a complete ... catalogue of the genes on chromosome 21. And we know that one or a few or all of these are the primary contributors to Down's syndrome." Reeves, a Down's syndrome investigator and professor of physiology at Johns Hopkins University in Baltimore, wrote an accompanying paper to the chromosome 21 report that will be released in Thursday's issue of the journal Nature.
Down's syndrome, the most common form of genetically caused mental retardation, occurs when a person is born with an extra, third copy of chromosome 21. It occurs in about one in 700 live births and can also cause congenital heart disease and Alzheimer's by age 40.
"For the first time," Reeves says, "we can define the playing field and who the players are on that field, and that's very, very important in allowing us to focus efforts in Down's syndrome."
The map may allow researchers to home in on specific genes in the chromosome that cause mental retardation in people with Down's 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," says David Patterson, PhD, president of the Eleanor Roosevelt Institute in Denver and chairman of the science advisory board of the National Down's Syndrome Society.
"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," says Francis Collins, MD, PhD, chairman of the Human Genome Project at the National Institutes of Health in Bethesda, Md. Patterson is involved in the project as well.
The German- and Japanese-led team that mapped both chromosomes is also part of the Human Genome Project, an international effort to break the chemical codes of the entire human genetic blueprint. Humans are normally born with 23 pairs of different chromosomes, which are made up of genes.
Chromosome 21 contains relatively few genes, but they are in a complex tangle.
"When one stares at a sequence like this, it makes you realize how complex it really is," says Huntington F. Willard, PhD, chairman of genetics at Case Western Reserve University in Cleveland. 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."
Reeves tells WebMD that this new information, combined with what is now known about chromosome 22, hints that humans may have only half of the 70,000 or 100,000 genes that scientists had speculated.
"To have the [chromosome] 21 consortium announce that there were only 225 genes is quite a surprise," Reeves adds. "In addition, they went another step and combined their information with that from chromosome 22, and they projected there may be only 40,000 human genes in all."
The researchers found that chromosome 21 contains far fewer genes than the 545 in chromosome 22, the second-smallest chromosome.
The map of chromosome 21 is 99.7% complete; technical limitations prevented a complete mapping, says Patterson.
Rudolph Tanzi, a professor of neurology at Harvard Medical School, said the chromosome map could eventually shed light on why people with Down's syndrome have very low rates 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 a while 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 to 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.