SRA

Background Since the availability of the rat reference genome in 2003, whole-genome sequencing data from more than 40 rat strains have become available. This data represents the broad range of strains that are used in rat research including several substrains. This genetic source of data harbors a wealth of information, but can now not be used to its full extent because of the use of different variant calling algorithms. In addition, all rat whole genome sequencing studies to date used the RGSC3.4 assembly, which is available since 2004. Furthermore, as mixed use of substrains occurs worldwide, characterization of substrain variants is important for proper interpretation of experimental data from different labs. Results Here we present a comprehensive, multi-sample and uniformly called set of genetic variation in 40 rat strains, including 19 substrains. We compare the sequences to a recent version of the rat reference assembly: RGSC5.0, which is available since 2012. In total we identified over 12 million genomic variants (SNVs, indels and structural variants) among the 40 strains. We identify 28,318 SNVs specific to substrains, which can be explained by introgression from other strains and ongoing evolution by genetic drift. Substrain SNVs tend to have a larger functional impact than older shared SNVs. Conclusions In summary we present a comprehensive universally analyzed catalog of genetic variants among 40 widely used rat inbred strains based on the RGSC5.0 assembly. This variant resource is valuable for a broad range of rat researchers and will promote further research in rat functional genomic research. In line with previous observations, our genome-wide analyses do not provide evidence for contribution of multiple ancestral founder rat subspecies to the currently used rat inbred strains, such as known for laboratory mice. 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.