An Ohio State University study published in March highlights the complexity of the effects of increased “gene dosage” that comes with Trisomy 21 . The researchers observed that a protein, MeCP2, involved in gene functions that influence cognition is reduced in brain tissue from people with Down syndrome. They then demonstrated that the levels of MeCP2 could be increased in the brains of mouse-models of Down syndrome, by injecting an experimental drug. The relative importance of MeCP2 in cognitive impairment in Down syndrome is not yet clear, although it is known to play a role in Rett’s syndrome.
The broader concepts of gene-protein product pathways acting in paradoxical ways is not really new, but the demonstration that increased gene dosage is not necessarily a simple linear effect in Trisomy 21 is significant for understanding that it is unlikely that there will be a simple “solution” to the anomalies that Trisomy 21 causes, even in isolated aspects of its multiple impacts. Even when we know what the genes involved are and what effects they have, the biological pathways are complex.
The online science news service Eureka reported the research and the interesting background to how the protein was linked to Trisomy 21 here.
Donald E. Kuhn, Gerard J. Nuovo, Alvin V. Terry Jr., Mickey M. Martin‡, Geraldine E. Malana, Sarah E. Sansom, Adam P. Pleister, Wayne D. Beck, Elizabeth Head, David S. Feldman and Terry S. Elton, Chromosome 21-derived MicroRNAs Provide an Etiological Basis for Aberrant Protein Expression in Human Down Syndrome Brains J. Biol. Chem. 2010 285: 1529-1543.
The abstract is available online from the journal's website.