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Scientists Uncover Patterns Of Genetic Changes In Mental Retardation

Researchers at Radboud University Medical Centre, together with UK Medical Research Council scientists at Oxford University, have uncovered some of the central characteristics of genes underlying mental retardation. The research, which shortens the list of genes whose changes lead to this disorder from thousands to several dozen, is published June 26 in the open-access journal PLoS Genetics. Mental retardation, which affects approximately two percent of the population, is often caused by many different, yet individually rare DNA deletions and duplications. Pinpointing the DNA changes responsible has proven challenging precisely because these changes are not concentrated in a small number of genes. The scientists took DNA from over 150 individuals with mental retardation and compared it with descriptions of 5,000 mice whose genomes each had single genes disrupted. The researchers found that the DNA changes associated with mental retardation contained greater than expected numbers of genes whose loss in mice also affected the nervous system. The large amounts of data from humans and mice were critical in revealing a relatively small set of genes that are relevant to mental retardation in humans. This study provides strong evidence that genomic deletions and duplications frequently cause mental retardation. By narrowing down the list of genes linked to the disorder, the research will help to enable genetic testing and diagnosis. In the future, the approach used in this study could also prove effective in highlighting genes altered in other medical conditions such as schizophrenia and autism. In some countries, including the UK, mental retardation is more properly referred to by clinicians as learning difficulty. The following organisations provided funding for this work: UK Medical Research Council, Berrow Lord Florey scholarship, the Swiss National Science Foundation, the Netherlands Organisation for Health Research and Development, and the EU-sponsored AnEUploidy project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CITATION: "Forging Links between Human Mental Retardation-Associated CNVs and Mouse Gene Knockout Models". Webber C, Hehir-Kwa JY, Nguyen D-Q, de Vries BBA, Veltman JA, et al. (2009) PLoS Genet 5(6): e1000531. doi:10.1371/journal.pgen.1000531 The Public Library of Science (PLoS)


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