Down syndrome affects about one in 700 babies born each year and is characterized by the presence of three copies of chromosome 21. In some rare cases, dubbed segmental trisomy, only a specific section of the chromosome is present in triplicate. As a result, many scientists studying the condition considered genes found in that region of the chromosome suspect in the disorder. But findings published today in the journal Science indicate that the cause of the disease may be more complicated than previously thought.

Roger Reeves of the Johns Hopkins School of Medicine and his colleagues bred mice to have one, two or three copies of the mouse equivalent of human chromosome 21. In addition, some animals had three copies of only the so-called Down syndrome critical region (DSCR). The researchers then compared these animals to the established mouse model of Down syndrome. Mice with three copies of DSCR, which contains some 33 genes, stood out as different. These mice weren't normal, but they weren't Down syndrome mice, either, Reeves says. Their faces were longer and narrower than normal, but Down syndrome is characterized by shorter than normal facial bones. What is more, some animals carrying only two copies of DSCR but three copies of the remainder of chromosome 21 did have the characteristic short bones of Down syndrome, which indicates that the presence of three versions of the DSCR is not necessary for Down-syndromelike features to develop.

In an accompanying commentary, David L. Nelson and Richard A. Gibbs of the Baylor College of Medicine note that the findings refute the notion that possessing three copies of the DSCR is the sole cause of the cranial and facial features of Down syndrome. For their part, Reeves and his colleagues posit that genes contained in the DSCR interacting with other genes could be to blame. The simplistic idea that just one of the hundreds of genes on chromosome 21 affect development no longer holds up, Reeves remarks. Now researchers can take a deep breath, accept that the syndrome is complex, and move forward.