Title |
A de novo paradigm for mental retardation
|
---|---|
Published in |
Nature Genetics, November 2010
|
DOI | 10.1038/ng.712 |
Pubmed ID | |
Authors |
Lisenka E L M Vissers, Joep de Ligt, Christian Gilissen, Irene Janssen, Marloes Steehouwer, Petra de Vries, Bart van Lier, Peer Arts, Nienke Wieskamp, Marisol del Rosario, Bregje W M van Bon, Alexander Hoischen, Bert B A de Vries, Han G Brunner, Joris A Veltman |
Abstract |
The per-generation mutation rate in humans is high. De novo mutations may compensate for allele loss due to severely reduced fecundity in common neurodevelopmental and psychiatric diseases, explaining a major paradox in evolutionary genetic theory. Here we used a family based exome sequencing approach to test this de novo mutation hypothesis in ten individuals with unexplained mental retardation. We identified and validated unique non-synonymous de novo mutations in nine genes. Six of these, identified in six different individuals, are likely to be pathogenic based on gene function, evolutionary conservation and mutation impact. Our findings provide strong experimental support for a de novo paradigm for mental retardation. Together with de novo copy number variation, de novo point mutations of large effect could explain the majority of all mental retardation cases in the population. |
X Demographics
Geographical breakdown
Country | Count | As % |
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France | 1 | 25% |
United States | 1 | 25% |
Australia | 1 | 25% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Scientists | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 12 | 2% |
United Kingdom | 12 | 2% |
Belgium | 5 | <1% |
Italy | 4 | <1% |
Brazil | 4 | <1% |
Germany | 3 | <1% |
Netherlands | 3 | <1% |
Canada | 3 | <1% |
France | 2 | <1% |
Other | 8 | 1% |
Unknown | 695 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 182 | 24% |
Researcher | 144 | 19% |
Student > Master | 83 | 11% |
Student > Bachelor | 51 | 7% |
Professor | 41 | 5% |
Other | 156 | 21% |
Unknown | 94 | 13% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 272 | 36% |
Biochemistry, Genetics and Molecular Biology | 135 | 18% |
Medicine and Dentistry | 128 | 17% |
Neuroscience | 32 | 4% |
Psychology | 18 | 2% |
Other | 57 | 8% |
Unknown | 109 | 15% |