Exome sequencing identifies the cause of a mendelian disorder View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-01

AUTHORS

Sarah B Ng, Kati J Buckingham, Choli Lee, Abigail W Bigham, Holly K Tabor, Karin M Dent, Chad D Huff, Paul T Shannon, Ethylin Wang Jabs, Deborah A Nickerson, Jay Shendure, Michael J Bamshad

ABSTRACT

We demonstrate the first successful application of exome sequencing to discover the gene for a rare mendelian disorder of unknown cause, Miller syndrome (MIM%263750). For four affected individuals in three independent kindreds, we captured and sequenced coding regions to a mean coverage of 40x and sufficient depth to call variants at approximately 97% of each targeted exome. Filtering against public SNP databases and eight HapMap exomes for genes with two previously unknown variants in each of the four individuals identified a single candidate gene, DHODH, which encodes a key enzyme in the pyrimidine de novo biosynthesis pathway. Sanger sequencing confirmed the presence of DHODH mutations in three additional families with Miller syndrome. Exome sequencing of a small number of unrelated affected individuals is a powerful, efficient strategy for identifying the genes underlying rare mendelian disorders and will likely transform the genetic analysis of monogenic traits. More... »

PAGES

30-35

Journal

TITLE

Nature Genetics

ISSUE

1

VOLUME

42

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.499

DOI

http://dx.doi.org/10.1038/ng.499

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021123766

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19915526


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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326 https://www.grid.ac/institutes/grid.34477.33 schema:alternateName University of Washington
327 schema:name Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
328 Department of Pediatrics, University of Washington, Seattle, Washington, USA.
329 rdf:type schema:Organization
330 https://www.grid.ac/institutes/grid.64212.33 schema:alternateName Institute for Systems Biology
331 schema:name Institute of Systems Biology, Seattle, Washington, USA.
332 rdf:type schema:Organization
 




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