Signs of Down syndrome found early in cell development
Last Updated: Friday, September 5, 2008 | 1:18 PM ET
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Down syndrome may result from early developmental changes in embryonic stem cells, according to researchers who hope the genetic findings could lead to new therapies.
People with Down syndrome carry an extra copy, or extra parts, of chromosome 21. In Thursday's online issue of the American Journal of Human Genetics, British researchers report how, in embryonic mouse stem cells, the extra chromosome disturbs a key regulatory gene, setting off a domino effect in other genes that control normal development.
Dean Nizetic, a professor of cellular and molecular biology at Barts and the London School of Medicine and Dentistry, led the team of researchers from the United States, Australia, Spain and Switzerland.
"We hope that further research might lead to clues for the design of new therapeutic approaches tackling developmental delay, mental retardation, ageing and regeneration of brain cells, and Alzheimer's disease," Nizetic said in a release.
"In other words, we hope our work will open new routes to tackle the genetics of these health disorders."
The researchers found that an extra chromosome 21 disturbs the key regulatory gene called Rest, and that one gene on chromosome 21 called DYRK1A acts as a trigger for the disturbance.
"We show that specifically silencing the third copy of DYRK1A rescues Rest levels," the researchers wrote in the study.
To make the discovery, the researchers used embryonic stem cells from a species of mouse genetically engineered to carry a copy of human chromosome 21.
About one in 800 babies in Canada are born with Down syndrome, the Canadian Down Syndrome Society says. Mental and physical development are generally slower in people with the condition, although many live productive lives into adulthood. Because of congenital complications like heart malformations and early-onset dementia, life expectancy is somewhat shorter.
Chromosome 21 contains around 300 genes. Scientists are gradually discovering how individual genes on the chromosome contribute to the symptoms of Down.
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