Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome

Published on Sep 1, 2010in Nature Genetics27.603
· DOI :10.1038/NG.646
Sarah B. Ng14
Estimated H-index: 14
(UW: University of Washington),
Abigail W. Bigham25
Estimated H-index: 25
(UW: University of Washington)
+ 18 AuthorsJay Shendure135
Estimated H-index: 135
(UW: University of Washington)
Sources
Abstract
Jay Shendure and colleagues report exome sequencing of ten individuals with Kabuki syndrome. They identify mutations in MLL2, encoding a Trithorax-group histone methyltransferase, as causal for this rare autosomal dominant malformation disorder.
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200942.78Nature
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Identifying disease-causing genetic variants in individual human genomes is a major challenge, even in protein-coding exons (the `exome'). Analysis of nucleotide-level sequence conservation may help address this challenge, on the assumption that purifying selection `constrains' evolutionary divergence at phenotypically important nucleotides. In contrast to functional classifiers (for example, non-synonymous mutations), constraint scores are quantitative and applicable to any genomic position1. H...
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Although DNA sequencing costs have fallen dramatically, they are still too high for whole genome sequencing to be used to routinely identify rare and novel variants in large cohorts. The targeted capture and massively parallel sequencing of the exomes of 12 humans is now reported. Freeman–Sheldon syndrome is used as a proof-of-concept that candidate genes for monogenic disorders can be identified by exome sequencing of a small number of unrelated, affected individuals.
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