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

Daniel C Ciobanu

Deanna M Church

Donald B Thomason

JL Peirce

John A Capra

Katherine S Pollard

Khyobeni Mozhui

Lu Lu

Megan K Mulligan

RH Waterston

Richa Agarwala

Robert W Williams

Stanley F Nelson

Williams L Taylor

Xusheng Wang

Zhengsheng Li

Zugen Chen

English

PubMed

Springer - Publisher Connector

High-throughput sequencing of the DBA/2J mouse genome

Nelson Stanley F

Pollard Katherine S

Mulligan Megan K

Mozhui Khyobeni

Li Zhengsheng

Ciobanu Daniel C

Church Deanna M

Chen Zugen

Capra John A

Agarwala Richa

Wang Xusheng

Taylor Williams L

Thomason Donald B

Williams Robert W

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BMC Bioinformatics

Wang, Xusheng

Agarwala, Richa

Capra, John A.

Chen, Zugen

Church, Deanna M.

Ciobanu, Daniel C.

Li, Zhengsheng

Lu, Lu

Mozhui, Khyobeni

Mulligan, Megan K.

Nelson, Stanley F.

Pollard, Katherine S.

Taylor, Williams L.

Thomason, Donald B.

Williams, Robert W.

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University of Nebraska - Lincoln 
DigitalCommons@University of Nebraska - Lincoln 
Faculty Papers and Publications in Animal 
Science Animal Science Department 
2010 
High-throughput sequencing of the DBA/2J mouse genome 
Xusheng Wang 
University of Tennessee Health Science Center 
Richa Agarwala 
National Institutes of Health 
John A. Capra 
University of California - San Francisco 
Zugen Chen 
University of California - Los Angeles 
Deanna M. Church 
National Institutes of Health 
See next page for additional authors 
Follow this and additional works at: https://digitalcommons.unl.edu/animalscifacpub 
 Part of the Animal Sciences Commons 
Wang, Xusheng; Agarwala, Richa; Capra, John A.; Chen, Zugen; Church, Deanna M.; Ciobanu, Daniel C.; Li, 
Zhengsheng; Lu, Lu; Mozhui, Khyobeni; Mulligan, Megan K.; Nelson, Stanley F.; Pollard, Katherine S.; Taylor, 
Williams L.; Thomason, Donald B.; and Williams, Robert W., "High-throughput sequencing of the DBA/2J 
mouse genome" (2010). Faculty Papers and Publications in Animal Science. 753. 
https://digitalcommons.unl.edu/animalscifacpub/753 
This Article is brought to you for free and open access by the Animal Science Department at 
DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Faculty Papers and 
Publications in Animal Science by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. 
Authors 
Xusheng Wang, Richa Agarwala, John A. Capra, Zugen Chen, Deanna M. Church, Daniel C. Ciobanu, 
Zhengsheng Li, Lu Lu, Khyobeni Mozhui, Megan K. Mulligan, Stanley F. Nelson, Katherine S. Pollard, 
Williams L. Taylor, Donald B. Thomason, and Robert W. Williams 
This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/
animalscifacpub/753 
ORAL PRESENTATION Open Access
High-throughput sequencing of the DBA/2J
mouse genome
Xusheng Wang1, Richa Agarwala2, John A Capra3, Zugen Chen4, Deanna M Church2, Daniel C Ciobanu5,
Zhengsheng Li1, Lu Lu1, Khyobeni Mozhui1, Megan K Mulligan1, Stanley F Nelson4, Katherine S Pollard3,
Williams L Taylor1, Donald B Thomason1, Robert W Williams1*
From UT-ORNL-KBRIN Bioinformatics Summit 2010
Cadiz, KY, USA. 19-21 March 2010
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 gen-
ome of DBA/2J using SOLiD and Illumina high
throughput short read protocols to generate a compre-
hensive 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-gen-
ome short reads of DBA/2J females using Illumina GA2
and ABI SOLiD massively parallel DNA sequencing
platforms. Comparing to the C57BL/6J reference gen-
ome sequence, we identified over 4.5 million single
nucleotide polymorphisms (SNPs), including 84 non-
sense 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 inver-
sions 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).
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 mod-
els. The sequence data provide a novel resource with
which to initiate reverse genetic analysis of complex
* Correspondence: rwilliam@nb.uthsc.edu
1University of Tennessee Health Science Center, Memphis, TN 38163, USA
Figure 1 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.
Wang et al. BMC Bioinformatics 2010, 11(Suppl 4):O7
http://www.biomedcentral.com/1471-2105/11/S4/O7
© 2010 Williams et al; licensee BioMed Central Ltd.
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 gen-
erated using BXD strains and any other cross involving
these two common parental strains.
Author details
1University of Tennessee Health Science Center, Memphis, TN 38163, USA.
2National Center for Biotechnology Information, National Library of Medicine,
National Institutes of Health, Bethesda, MD 20894, USA. 3Gladstone Institutes,
University of California, San Francisco, CA 94158, USA. 4University of
California, Los Angeles, CA 90095, USA. 5University of Nebraska, Lincoln, NE
68588, USA.
Published: 23 July 2010
References
1. Peirce JL, Lu L, Gu J, Silver LM, Williams RW: A new set of BXD
recombinant inbred lines from advanced intercross populations in mice.
BMC genetics 2004, 5:7.
2. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P,
Agarwala R, Ainscough R, Alexandersson M, An P: Initial sequencing and
comparative analysis of the mouse genome. Nature 2002,
420(6915):520-562.
doi:10.1186/1471-2105-11-S4-O7
Cite this article as: Wang et al.: High-throughput sequencing of the
DBA/2J mouse genome. BMC Bioinformatics 2010 11(Suppl 4):O7.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Wang et al. BMC Bioinformatics 2010, 11(Suppl 4):O7
http://www.biomedcentral.com/1471-2105/11/S4/O7
Page 2 of 2


High-throughput sequencing of the DBA/2J
mouse genome

DigitalCommons@University of Nebraska

University of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Faculty Papers and Publications in Animal Science Animal Science Department 2010 High-throughput sequencing of the DBA/2J mouse genome Xusheng Wang University of Tennessee Health Science Center Richa Agarwala National Institutes of Health John A. Capra University of California - San Francisco Zugen Chen University of California - Los Angeles Deanna M. Church National Institutes of Health See next page for additional authors Follow this and additional works at: https://digitalcommons.unl.edu/animalscifacpub  Part of the Animal Sciences Commons Wang, Xusheng; Agarwala, Richa; Capra, John A.; Chen, Zugen; Church, Deanna M.; Ciobanu, Daniel C.; Li, Zhengsheng; Lu, Lu; Mozhui, Khyobeni; Mulligan, Megan K.; Nelson, Stanley F.; Pollard, Katherine S.; Taylor, Williams L.; Thomason, Donald B.; and Williams, Robert W., "High-throughput sequencing of the DBA/2J mouse genome" (2010). Faculty Papers and Publications in Animal Science. 753. https://digitalcommons.unl.edu/animalscifacpub/753 This Article is brought to you for free and open access by the Animal Science Department at DigitalCommons@University of Nebraska - Lincoln. It has been accepted for inclusion in Faculty Papers and Publications in Animal Science by an authorized administrator of DigitalCommons@University of Nebraska - Lincoln. Authors Xusheng Wang, Richa Agarwala, John A. Capra, Zugen Chen, Deanna M. Church, Daniel C. Ciobanu, Zhengsheng Li, Lu Lu, Khyobeni Mozhui, Megan K. Mulligan, Stanley F. Nelson, Katherine S. Pollard, Williams L. Taylor, Donald B. Thomason, and Robert W. Williams This article is available at DigitalCommons@University of Nebraska - Lincoln: https://digitalcommons.unl.edu/animalscifacpub/753 ORAL PRESENTATION Open AccessHigh-throughput sequencing of the DBA/2Jmouse genomeXusheng Wang1, Richa Agarwala2, John A Capra3, Zugen Chen4, Deanna M Church2, Daniel C Ciobanu5,Zhengsheng Li1, Lu Lu1, Khyobeni Mozhui1, Megan K Mulligan1, Stanley F Nelson4, Katherine S Pollard3,Williams L Taylor1, Donald B Thomason1, Robert W Williams1*From UT-ORNL-KBRIN Bioinformatics Summit 2010Cadiz, KY, USA. 19-21 March 2010BackgroundThe DBA/2J mouse is not only the oldest inbred strain,but also one of the most widely used strains. DBA/2Jexhibits many unique anatomical, physiological, andbehavior traits. In addition, DBA/2J is one parent of thelarge BXD family of recombinant inbred strains [1]. Thegenome of the other parent of this BXD family—C57BL/6J—has been sequenced and serves as themouse reference genome [2]. We sequenced the gen-ome of DBA/2J using SOLiD and Illumina highthroughput short read protocols to generate a compre-hensive set of ~5 million sequence variants segregatingin the BXD family that ultimately cause developmental,anatomical, functional and behavioral differences amongthese 80+ strains.ResultsWe generated approximately 13.2 and 38.9× whole-gen-ome short reads of DBA/2J females using Illumina GA2and ABI SOLiD massively parallel DNA sequencingplatforms. Comparing to the C57BL/6J reference gen-ome sequence, we identified over 4.5 million singlenucleotide polymorphisms (SNPs), including 84 non-sense and ~11,000 missense mutations, 78% of whichare novel. We also detected ~568,000 insertions anddeletions (indels) within single short reads and ~9,400between mate-paired reads. Approximately 300 inver-sions were detected by SOLiD mate-pair reads, 46 ofwhich span at least one exon. In addition, we identified~22,000 copy number variants (CNVs) in the range of1 Kb to 100 Kb (Figure 1).ConclusionOur study generates the first consensus sequence for theDBA/2J and creates a compendium of sequence andstructural variations that will be used by the communityof researchers who study complex traits in mouse mod-els. The sequence data provide a novel resource withwhich to initiate reverse genetic analysis of complex* Correspondence: rwilliam@nb.uthsc.edu1University of Tennessee Health Science Center, Memphis, TN 38163, USAFigure 1 Concentric circles represent the sequence andstructural variation across mouse chromosomes. Moving inwardfrom the outer circle, circle 1 denotes each chromosome. Circle 2,read depth with 100kb window. Circle 3, SNP density with 100kbwindows (black is lowest density and orange is highest density).Circle 4, Indels density with 100kb window. Circle 4, Inversion. Circle5, CNVs, blue (outward) denotes loss of CNVs and green (inward)denotes gains of CNVs.Wang et al. BMC Bioinformatics 2010, 11(Suppl 4):O7http://www.biomedcentral.com/1471-2105/11/S4/O7© 2010 Williams et al; licensee BioMed Central Ltd.traits, particularly by exploiting strong alleles (prematurestop codons, frame-shift mutations, and deletion) thatdifferentially affect members of the BXD strain family.The DBA/2J genome is also an essential prerequisite tounbiased alignment of RNA-seq and ChIP-seq data gen-erated using BXD strains and any other cross involvingthese two common parental strains.Author details1University of Tennessee Health Science Center, Memphis, TN 38163, USA.2National Center for Biotechnology Information, National Library of Medicine,National Institutes of Health, Bethesda, MD 20894, USA. 3Gladstone Institutes,University of California, San Francisco, CA 94158, USA. 4University ofCalifornia, Los Angeles, CA 90095, USA. 5University of Nebraska, Lincoln, NE68588, USA.Published: 23 July 2010References1. Peirce JL, Lu L, Gu J, Silver LM, Williams RW: A new set of BXDrecombinant inbred lines from advanced intercross populations in mice.BMC genetics 2004, 5:7.2. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P,Agarwala R, Ainscough R, Alexandersson M, An P: Initial sequencing andcomparative analysis of the mouse genome. Nature 2002,420(6915):520-562.doi:10.1186/1471-2105-11-S4-O7Cite this article as: Wang et al.: High-throughput sequencing of theDBA/2J mouse genome. BMC Bioinformatics 2010 11(Suppl 4):O7.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitWang et al. BMC Bioinformatics 2010, 11(Suppl 4):O7http://www.biomedcentral.com/1471-2105/11/S4/O7Page 2 of 2

ORAL PRESENTATION Open Access
High-throughput sequencing of the DBA/2J
mouse genome
Xusheng Wang1, Richa Agarwala2, John A Capra3, Zugen Chen4, Deanna M Church2, Daniel C Ciobanu5,
Zhengsheng Li1, Lu Lu1, Khyobeni Mozhui1, Megan K Mulligan1, Stanley F Nelson4, Katherine S Pollard3,
Williams L Taylor1, Donald B Thomason1, Robert W Williams1*
From UT-ORNL-KBRIN Bioinformatics Summit 2010
Cadiz, KY, USA. 19-21 March 2010
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 gen-
ome of DBA/2J using SOLiD and Illumina high
throughput short read protocols to generate a compre-
hensive 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-gen-
ome short reads of DBA/2J females using Illumina GA2
and ABI SOLiD massively parallel DNA sequencing
platforms. Comparing to the C57BL/6J reference gen-
ome sequence, we identified over 4.5 million single
nucleotide polymorphisms (SNPs), including 84 non-
sense 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 inver-
sions 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).
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 mod-
els. The sequence data provide a novel resource with
which to initiate reverse genetic analysis of complex
* Correspondence: rwilliam@nb.uthsc.edu
1University of Tennessee Health Science Center, Memphis, TN 38163, USA
Figure 1 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.
Wang et al. BMC Bioinformatics 2010, 11(Suppl 4):O7
http://www.biomedcentral.com/1471-2105/11/S4/O7
© 2010 Williams et al; licensee BioMed Central Ltd.
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 gen-
erated using BXD strains and any other cross involving
these two common parental strains.
Author details
1University of Tennessee Health Science Center, Memphis, TN 38163, USA.
2National Center for Biotechnology Information, National Library of Medicine,
National Institutes of Health, Bethesda, MD 20894, USA. 3Gladstone Institutes,
University of California, San Francisco, CA 94158, USA. 4University of
California, Los Angeles, CA 90095, USA. 5University of Nebraska, Lincoln, NE
68588, USA.
Published: 23 July 2010
References
1. Peirce JL, Lu L, Gu J, Silver LM, Williams RW: A new set of BXD
recombinant inbred lines from advanced intercross populations in mice.
BMC genetics 2004, 5:7.
2. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P,
Agarwala R, Ainscough R, Alexandersson M, An P: Initial sequencing and
comparative analysis of the mouse genome. Nature 2002,
420(6915):520-562.
doi:10.1186/1471-2105-11-S4-O7
Cite this article as: Wang et al.: High-throughput sequencing of the
DBA/2J mouse genome. BMC Bioinformatics 2010 11(Suppl 4):O7.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Wang et al. BMC Bioinformatics 2010, 11(Suppl 4):O7
http://www.biomedcentral.com/1471-2105/11/S4/O7
Page 2 of 2


Crossref

An P: Initial sequencing and comparative analysis of the mouse genome.

RW: A new set of BXD recombinant inbred lines from advanced intercross populations in mice. BMC genetics

Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance

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High-throughput sequencing of the DBA/2J mouse genome

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