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Old 04-25-2012, 04:30 AM   #1
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Default RNA-Seq: High levels of RNA-editing site conservation amongst 15 laboratory mouse str

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High levels of RNA-editing site conservation amongst 15 laboratory mouse strains.

Genome Biol. 2012 Apr 23;13(4):R26

Authors: Daneck P, Nellaker C, McIntyre RE, Buendia-Buendia JE, Bumpstead S, Ponting CP, Flint J, Durbin R, Keane TM, Adams DJ

Abstract
ABSTRACT: BACKGROUND: Adenosine-to-inosine (A-to-I) editing is a site-selective post-transcriptional alteration of double-stranded RNA by ADAR deaminases that is crucial for homeostasis and development. Recently the Mouse Genomes Project generated genome sequences for 17 laboratory mouse strains and rich catalogues of variants. We also generated RNA-seq data from whole brain RNA from 15 of the sequenced strains. RESULTS: Here we present a computational approach that takes an initial set of transcriptome/genome mismatch sites and filters these calls taking into account systematic biases in alignment, single nucleotide variant (SNV) calling, and sequencing depth to identify RNA editing sites with high accuracy. We applied this approach to our panel of mouse strain transcriptomes identifying 7,389 editing sites with an estimated false-discovery rate of between 2.9-10.5%. The overwhelming majority of these edits were of the A-to-I type with less than 2.4% not of this class, and only 3 of these edits could not be explained as alignment artefacts. We validated 24 novel RNA editing sites in coding sequence including two non-synonymous edits in the Cacna1d gene that fell into the IQ domain portion of the Cav1.2 voltage-gated calcium channel indicating a potential role for editing in the generation of transcript diversity. CONCLUSIONS: We show that despite over two million years of evolutionary divergence the sites edited and the level of editing at each site is remarkably consistent across the 15 strains. In the Cds2 gene we find evidence for RNA-editing acting to preserve the ancestral transcript sequence despite genomic sequence divergence.


PMID: 22524474 [PubMed - as supplied by publisher]



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