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Publication year
2010Source
Nature Genetics, 42, 12, (2010), pp. 1109-12ISSN
Annotation
01 december 2010
Publication type
Article / Letter to editor
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Organization
Human Genetics
Journal title
Nature Genetics
Volume
vol. 42
Issue
iss. 12
Page start
p. 1109
Page end
p. 12
Subject
IGMD 3: Genomic disorders and inherited multi-system disorders; NCMLS 6: Genetics and epigenetic pathways of diseaseAbstract
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.
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- Faculty of Medical Sciences [90373]
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