December 11, 2002
Geneva, Switzerland (Dec. 5th)—In an effort to determine how certain genes operate, researchers from Switzerland stumbled upon something quite unexpected: Comparing the entire human sequence of chromosome 21 to a similar region in the mouse, they discovered that the identical DNA segments found in the two species were not actually in the genes. Instead, the genetic similarities stemmed from DNA that doesn’t code for proteins, or the so-called non-genes, which may help control the actions and structure of the genes that are thought to do much of the real work.
The exact role non-genes play is still unclear, according to a study in the journal Nature, but the findings suggest that mutations to these largely ignored genetic regions may also lead to disease. Alterations to chromosome 21 are directly linked to Down syndrome and trisomy 21, and may be a partially responsible for several other disorders, including bipolar disease and certain types of cancer.
"These non-genes are clearly more important than anyone has realized,” said the study’s lead author, Dr. Stylianos Antonarakis, of the Division of Medical Genetics at the University of Geneva Medical School. "And if they are altered or damaged, they may serve as another stimulus for many common genetic disorders."
The results add further complexity to our understanding of genes, a problem inadvertently made worse with the decoding of various genomes. To figure out how genes work, researchers have increasingly turned to comparative studies using different species. The human and mouse genome make for an excellent comparison, for instance, since they share many of the same genes.
As part of their study, Dr. Antonarakis and colleagues from the Ludwig Institute for Cancer Research identified a total of 3,491 conserved DNA segments in both the human and related mouse chromosomes. Of these, roughly 1,200 were clearly genes. After reviewing genetic databases and then painstakingly verifying each DNA sequence, the researchers found that the remaining segments probably acted in some regulatory fashion, but they were too different to be classified as actual genes. Nevertheless, this closely related material provides further clues for deciphering the genetic causes of disease.
"These non-gene regions may also be important in trying to understand trisomy 21 or Down Syndrome,” said Dr. Antonarakis. "Although we only looked at chromosome 21, we suspect that same is true for other genetic disorders."
By Eric Sabo
Reymond A, Marigo V, Yaylaoglu MB, Leoni A, Ucla C, Scamuffa N, Caccioppoli C, Dermitzakis ET, Lyle R, Banfi S, Eichele G, Antonarakis SE, Ballabio A. Human chromosome 21 gene expression atlas in the mouse. Nature. 2002 Dec 5;420(6915):582-6. [PMID: 12466854]