In the fast and furious race to decode the human genome, the smallest entrant—human chromosome 21—is second to cross the finish line. The result could eventually be a big victory for people with Down’s syndrome, scientists say.
Down’s syndrome is the most common genetic disorder; 1 in every 700 babies is born with it. It’s caused by an extra copy of chromosome 21, so the disorder is also known as trisomy 21. Embryos with three copies of other chromosomes, except X and Y, don’t survive to birth.
“There’s something special about 21,” says Ian Dunham of the Sanger Centre in Cambridge, England. That something special, scientists have long suspected, is a paucity of genes. “We’ve known for the past few years that this chromosome would have less than its share,” says Roger H. Reeves, a geneticist at Johns Hopkins Medical Institutions in Baltimore, Md.
Still, the researchers were surprised to find only 225 genes on the tiny chromosome, says Katheleen Gardiner, a molecular biologist at the Eleanor Roosevelt Institute in Denver. She is part of the international sequencing consortium that includes researchers from Japan, Germany, France, Switzerland, England, and the United States.
Chromosome 22 is only slightly larger than chromosome 21 but contains at least 545 genes (SN: 12/4/99, p. 356). The researchers have probably missed some genes on chromosome 21, says Gardiner, but “it’s not like we’re missing half of them, or even 30 percent.” She estimates that the gene count is off by less than 10 percent.
“Chromosome 21 is fascinating because it has something for everyone,” says Julie R. Korenberg of the University of California and Cedars-Sinai Medical Center, both in Los Angeles. Half the chromosome is relatively rich in genes, and the other half, impoverished, she says.
Researchers affectionately refer to the largest gene-poor region as “the Black Hole,” says Gardiner. It contains only 58 genes in 17 million DNA bases—1 gene in every 301,000 bases. The relatively gene-rich portion of the chromosome has 1 gene in 58,000 bases. Even this portion of the chromosome is poverty-stricken compared with the genome as a whole. On average, gene-rich regions have a gene every 9,000 bases, the researchers say, and gene-poor regions have 1 gene every 150,000 bases.
The small number of genes on chromosome 21 is “a gift,” says Korenberg. Fewer genes means fewer genetic insults for the body to handle, making it possible for people with an extra copy of the chromosome to survive to adulthood.
Eventually, researchers may devise ways to counteract the genes that cause some Down’s syndrome defects, Korenberg says. “We’re closer, but there aren’t going to be new therapies next week,” cautions Gardiner.
The results of the chromosome 21 study were published Monday on the Nature Web site and will appear in the May 18 print issue.
Data from chromosomes 21 and 22 suggest that the total human-gene count will be lower than estimated, the international team says.