1471-2105-11-S4-O7 1471-2105 Oral presentation <p>High-throughput sequencing of the DBA/2J mouse genome</p> Wang Xusheng Agarwala Richa Capra A John Chen Zugen Church M Deanna Ciobanu C Daniel Li Zhengsheng Lu Lu Mozhui Khyobeni Mulligan K Megan Nelson F Stanley Pollard S Katherine Taylor L Williams Thomason B Donald Williams W Robert rwilliam@nb.uthsc.edu

University of Tennessee Health Science Center, Memphis, TN 38163, USA

National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA

Gladstone Institutes, University of California, San Francisco, CA 94158, USA

University of California, Los Angeles, CA 90095, USA

University of Nebraska, Lincoln, NE 68588, USA

 BMC Bioinformatics <p>UT-ORNL-KBRIN Bioinformatics Summit 2010</p> Eric C Rouchka, Robert M Flight and Claire Rinehart Funding for the UT-ORNL-KBRIN Summit is provided in part by The Kentucky Biomedical Research Infrastructure Network (KBRIN), the University of Tennessee Molecular Resource Center, The UT-ORNL Science Alliance, The University of Tennessee Center for Integrative and Translational Genomics, and NIH grant P20RR16481. Meeting abstracts - A single PDF containing all abstracts in this Supplement is available here. http://www.biomedcentral.com/content/pdf/1471-2105-11-S4-info.pdf <p>UT-ORNL-KBRIN Bioinformatics Summit 2010</p> Cadiz, KY, USA 19-21 March 2010 http://www.lumins.com/summit10/ 1471-2105 2010 11 Suppl 4 O7 http://www.biomedcentral.com/1471-2105/11/S4/O7 10.1186/1471-2105-11-S4-O7 23 07 2010 2010 Williams et al; licensee BioMed Central Ltd.

Background

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 1. The genome of the other parent of this BXD family—C57BL/6J—has been sequenced and serves as the mouse reference genome 2. 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.

Results

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).

<p>Figure 1</p>

Concentric circles represent the sequence and structural variation across mouse chromosomes.

Concentric circles represent the sequence and structural variation across mouse chromosomes. Moving inward from the outer circle, circle 1 denotes each chromosome. Circle 2, read depth with 100kb window. Circle 3, SNP density with 100kb windows (black is lowest density and orange is highest density). Circle 4, Indels density with 100kb window. Circle 4, Inversion. Circle 5, CNVs, blue (outward) denotes loss of CNVs and green (inward) denotes gains of CNVs.

Conclusion

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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