title: High levels of RNA-editing site conservation amongst 15 laboratory mouse strains.
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 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 and 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 three of these edits could not be explained as alignment artifacts. 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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH, UK.
authors.forename: Petr
authors.initials: P
authors.lastname: Danecek
authors.forename: Christoffer
authors.initials: C
authors.lastname: Nellåker
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: McIntyre
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Buendia-Buendia
authors.forename: Suzannah
authors.initials: S
authors.lastname: Bumpstead
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.forename: Richard
authors.initials: R
authors.lastname: Durbin
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Keane
authors.forename: David J
authors.initials: DJ
authors.lastname: Adams
mesh_terms: D000818:Animals; D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D030561:Databases, Nucleic Acid; D016678:Genome; D060005:Genotyping Techniques; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017393:RNA Editing; D015203:Reproducibility of Results; D016415:Sequence Alignment / Q000379:methods; D017423:Sequence Analysis, RNA / Q000379:methods; D059467:Transcriptome; D020506:Untranslated Regions
chemical_list: C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type; D020506:Untranslated Regions