Genomic landscape of rat strain and substrain variation

Roel Hermsen, Joep de Ligt, Wim Spee, Francis Blokzijl, Sebastian Schäfer, Eleonora Adami, Sander Boymans, Stephen Flink, Ruben van Boxtel, Robin H van der Weide, Tim Aitman, Norbert Hübner, Marieke Simonis, Boris Tabakoff, Victor Guryev, Edwin Cuppen

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Since the completion of the rat reference genome in 2003, whole-genome sequencing data from more than 40 rat strains have become available. These data represent the broad range of strains that are used in rat research including commonly used substrains. Currently, this wealth of information cannot be used to its full extent, because the variety of different variant calling algorithms employed by different groups impairs comparison between strains. In addition, all rat whole genome sequencing studies to date used an outdated reference genome for analysis (RGSC3.4 released in 2004).

RESULTS: Here we present a comprehensive, multi-sample and uniformly called set of genetic variants in 40 rat strains, including 19 substrains. We reanalyzed all primary data using a recent version of the rat reference assembly (RGSC5.0 released in 2012) and identified over 12 million genomic variants (SNVs, indels and structural variants) among the 40 strains. 28,318 SNVs are specific to individual substrains, which may be explained by introgression from other unsequenced strains and ongoing evolution by genetic drift. Substrain SNVs may have a larger predicted functional impact compared to older shared SNVs.

CONCLUSIONS: In summary we present a comprehensive catalog of uniformly analyzed genetic variants among 40 widely used rat inbred strains based on the RGSC5.0 assembly. This represents a valuable resource, which will facilitate rat functional genomic research. In line with previous observations, our genome-wide analyses do not show evidence for contribution of multiple ancestral founder rat subspecies to the currently used rat inbred strains, as is the case for mouse. In addition, we find that the degree of substrain variation is highly variable between strains, which is of importance for the correct interpretation of experimental data from different labs.

Original languageEnglish
Pages (from-to)357
JournalBMC Genomics
Volume16
DOIs
Publication statusPublished - 6 May 2015

Keywords

  • Animals
  • Dogs
  • Evolution, Molecular
  • Genetic Drift
  • Genomics
  • INDEL Mutation
  • Mice
  • Polymorphism, Single Nucleotide
  • Rats
  • Species Specificity
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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