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Science 29 May 2009:
Vol. 324. no. 5931, pp. 1210 - 1213
DOI: 10.1126/science.1170995
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Reports

Genome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing

Jin Billy Li,1,* Erez Y. Levanon,1,* Jung-Ki Yoon,1,{dagger} John Aach,1 Bin Xie,2 Emily LeProust,3 Kun Zhang,1,{ddagger} Yuan Gao,2,4 George M. Church1,§

Adenosine-to-inosine (A-to-I) RNA editing leads to transcriptome diversity and is important for normal brain function. To date, only a handful of functional sites have been identified in mammals. We developed an unbiased assay to screen more than 36,000 computationally predicted nonrepetitive A-to-I sites using massively parallel target capture and DNA sequencing. A comprehensive set of several hundred human RNA editing sites was detected by comparing genomic DNA with RNAs from seven tissues of a single individual. Specificity of our profiling was supported by observations of enrichment with known features of targets of adenosine deaminases acting on RNA (ADAR) and validation by means of capillary sequencing. This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing–related human diseases.

1 Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
2 Center for the Study of Biological Complexity, Virginia Commonwealth University, 1000 West Cary Street, Richmond, VA 23284, USA.
3 Genomics Solution Unit, Agilent Technologies, 5301 Stevens Creek Boulevard, Santa Clara, CA 95051, USA.
4 Department of Computer Science, Virginia Commonwealth University, 401 West Main Street, Richmond, VA 23284, USA.

* These authors contributed equally to this work.

{dagger} Present address: College of Medicine, Seoul National University, Seoul 110-799, Korea.

{ddagger} Present address: Department of Bioengineering, University of California, San Diego, CA 92093, USA.

§ To whom correspondence should be addressed. E-mail: http://arep.med.harvard.edu/gmc/email.html

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