Their report in the Oct. 22 issue of Science, based on studies in genetically engineered mice, shreds a 30-year-old notion that genes in this region are largely responsible for the condition's characteristic facial features and some of its other common traits. Down syndrome, which affects roughly 1 in 700 live births, is the most common genetic cause of mental retardation and congenital heart disease.

"The simplistic idea that just one of the hundreds of genes on chromosome 21 affects development no longer holds up," says Roger Reeves, Ph.D., professor of molecular biology and genetics in Johns Hopkins' Institute for Basic Biomedical Sciences and McKusick-Nathans Institute of Genetic Medicine. "Now researchers can take a deep breath, accept that the syndrome is complex, and move forward."

Down syndrome occurs when three -- instead of two -- copies of chromosome 21 are present in a fertilized egg, although rare cases occur when a section of the chromosome -- rather than the whole chromosome -- is found in triplicate in a situation called segmental trisomy. A small region of this replicated segment is found in triplicate in all people with segmental trisomy and Down syndrome's facial features, and so it had been dubbed the "Down syndrome critical region" or DSCR. Proponents of DSCR's presumed role had focused on its consistency in people with segmental trisomy, but largely ignored the fact that no one with this condition has only that region in triplicate, Reeves says.

To see whether DSCR is as critical as many suggested, then-graduate student Lisa Olson, Ph.D., created "chromosomally" engineered mice, and found that mice with three copies of just their DSCR equivalent actually had facial and skeletal changes opposite of those seen in Down sy
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
21-Oct-2004