Abstract
Many clinical phenotypes occur sporadically despite genetics contributing partly or entirely to their cause. To what extent are de novo mutations the cause of sporadic traits? Locus-specific mutation rates for genomic rearrangements appear to be two to four orders of magnitude greater than nucleotide-specific rates for base substitutions. Widespread implementation of high-resolution genome analyses to detect de novo copy-number variation may identify the cause of traits previously intractable to conventional genetic analyses.
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Acknowledgements
I thank M. Hurles, P. Stankiewicz, A. Beaudet and members of my laboratory for thoughtful reviews. I apologize to colleagues and authors of relevant papers that could not be cited due to space limitations. My laboratory has been generously supported by the US National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Eye Institute, National Institute of Dental and Craniofacial Research, National Cancer Institute and National Institute of Child Health and Human Development), the Muscular Dystrophy Association, the Charcot-Marie-Tooth Association and the March of Dimes.
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Lupski, J. Genomic rearrangements and sporadic disease. Nat Genet 39 (Suppl 7), S43–S47 (2007). https://doi.org/10.1038/ng2084
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