High-throughput sequencing of the DBA/2J mouse genome
BMC Bioinformatics volume 11, Article number: O7 (2010)
The DBA/2J mouse is not only the oldest inbred strain, but also one of the most widely used strains. DBA/2J exhibits many unique anatomical, physiological, and behavior traits. In addition, DBA/2J is one parent of the large BXD family of recombinant inbred strains . The genome of the other parent of this BXD family—C57BL/6J—has been sequenced and serves as the mouse reference genome . We sequenced the genome of DBA/2J using SOLiD and Illumina high throughput short read protocols to generate a comprehensive set of ~5 million sequence variants segregating in the BXD family that ultimately cause developmental, anatomical, functional and behavioral differences among these 80+ strains.
We generated approximately 13.2 and 38.9× whole-genome short reads of DBA/2J females using Illumina GA2 and ABI SOLiD massively parallel DNA sequencing platforms. Comparing to the C57BL/6J reference genome sequence, we identified over 4.5 million single nucleotide polymorphisms (SNPs), including 84 nonsense and ~11,000 missense mutations, 78% of which are novel. We also detected ~568,000 insertions and deletions (indels) within single short reads and ~9,400 between mate-paired reads. Approximately 300 inversions were detected by SOLiD mate-pair reads, 46 of which span at least one exon. In addition, we identified ~22,000 copy number variants (CNVs) in the range of 1 Kb to 100 Kb (Figure 1).
Our study generates the first consensus sequence for the DBA/2J and creates a compendium of sequence and structural variations that will be used by the community of researchers who study complex traits in mouse models. The sequence data provide a novel resource with which to initiate reverse genetic analysis of complex traits, particularly by exploiting strong alleles (premature stop codons, frame-shift mutations, and deletion) that differentially affect members of the BXD strain family. The DBA/2J genome is also an essential prerequisite to unbiased alignment of RNA-seq and ChIP-seq data generated using BXD strains and any other cross involving these two common parental strains.
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Wang, X., Agarwala, R., Capra, J.A. et al. High-throughput sequencing of the DBA/2J mouse genome. BMC Bioinformatics 11 (Suppl 4), O7 (2010). https://doi.org/10.1186/1471-2105-11-S4-O7