Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2004 Apr;14(4):685-92.
doi: 10.1101/gr.2067704.

Automated whole-genome multiple alignment of rat, mouse, and human

Michael Brudno  1 , Alexander Poliakov, Asaf Salamov, Gregory M Cooper, Arend Sidow, Edward M Rubin, Victor Solovyev, Serafim Batzoglou, Inna Dubchak
Affiliations
Comparative Study

Automated whole-genome multiple alignment of rat, mouse, and human

Michael Brudno et al. Genome Res. 2004 Apr.

Abstract

We have built a whole-genome multiple alignment of the three currently available mammalian genomes using a fully automated pipeline that combines the local/global approach of the Berkeley Genome Pipeline and the LAGAN program. The strategy is based on progressive alignment and consists of two main steps: (1) alignment of the mouse and rat genomes, and (2) alignment of human to either the mouse-rat alignments from step 1, or the remaining unaligned mouse and rat sequences. The resulting alignments demonstrate high sensitivity, with 87% of all human gene-coding areas aligned in both mouse and rat. The specificity is also high: <7% of the rat contigs are aligned to multiple places in human, and 97% of all alignments with human sequence >100 kb agree with a three-way synteny map built independently, using predicted exons in the three genomes. At the nucleotide level <1% of the rat nucleotides are mapped to multiple places in the human sequence in the alignment, and 96.5% of human nucleotides within all alignments agree with the synteny map. The alignments are publicly available online, with visualization through the novel Multi-VISTA browser that we also present.

PubMed Disclaimer

Figures

Figure 1
Figure 1
General scheme of the method. White boxes show original and intermediate data; green boxes, mapping/alignment steps; and yellow and grey boxes, resulting data.
Figure 2
Figure 2
Exon-based map of conserved synteny between the rat, human, and mouse genomes. Each rat chromosome (presented along the x-axis) contains two columns, colored according to conserved synteny with chromosomes of the human and mouse genomes. Chromosome color scheme is shown at the bottom.
Figure 3
Figure 3
The chart shows the coverage of the three genomes and the RefSeq coding exons on the three genomes in our alignments using the thresholds from the Mouse genome comparisons (Waterston et al. 2002; Schwartz et al. 2003). The chart makes clear that although the bulk of the rat and mouse genomes can be confidently aligned to the other rodent, only a minority (35%-40%) is alignable to human. The percentage of each rodent genome that is aligned to human but not to the other rodent (0.4% of rat, 1.4% of mouse) is reflective of the fraction of the sequence missing in the other rodent.
Figure 4
Figure 4
APOA5 region (chr8:49261987-49270935) on the Rat Genome (June 2003, RGSC version 3.1, University of California, Santa Cruz, version rn3) displayed by Multi-VISTA Genome Browser (VGB2.0) accessible through the gateway at http://pipeline.lbl.gov. Conservation plots for human/rat (top plot) and mouse/rat (bottom plot) are displayed on the scale of the rat sequence. Conserved regions above the level of 70%/100 bp are highlighted under the curve, with red indicating a conserved noncoding region; blue, a conserved exon; and turquoise, untranslated region.
See this image and copyright information in PMC

References

    1. Altschul, S.F., Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, Z., Miller, W., and Lipman, D.J. 1997. Gapped BLAST and PSI-BLAST: A new generation of protein database search programs. Nucleic Acids Res. 25: 3389-3402. - PMC - PubMed
    1. Blanchette, M., Kent, W.J., Riemer, C., Elnitski, L., Smit, A.F.A., Roskin, K.M., Baertsch, R., Rosenbloom, K., Clawson, H., Green, E.D., et al. 2004. Aligning multiple genomic sequences with the threaded blockset aligner. Genome Res. (this issue). - PMC - PubMed
    1. Boffelli, D., McAuliffe, J., Ovcharenko, D., Lewis, K.D., Ovcharenko, I., Pachter, L., and Rubin, E.M. 2003. Phylogenetic shadowing of primate sequences to find functional regions of the human genome. Science 299: 1391-1394. - PubMed
    1. Brudno, M., Do, C.B., Cooper, G.M., Kim, M.F., Davydov, E., Green, E.D., Sidow, A., Batzoglou, S., and NISC Comparative Sequencing Program. 2003a. LAGAN and Multi-LAGAN: Efficient tools for large-scale multiple alignment of genomic DNA. Genome Res. 13: 721-731. - PMC - PubMed
    1. Brudno, M., Malde, S., Poliakov, A., Do, C.B., Couronne, O., Dubchak, I., and Batzoglou, S. 2003b. Glocal alignment: Finding rearrangements during alignment. Bioinformatics 19: 54i-62i. - PubMed

WEB SITE REFERENCES

    1. http://pipeline.lbl.gov/; Comparative analysis pipeline gateway at Lawrence Berkeley National Laboratory.
    1. http://lagan.stanford.edu/; LAGAN Toolkit Web site.
    1. http://genome.ucsc.edu/; University of California, Santa Cruz, Web site from which the human, mouse, and rat genome assemblies used in this study were downloaded.
    1. http://pipeline.lbl.gov/downloads.shtml; Download page for whole genome alignments and other materials.
    1. http://www.softberry.com/berry.phtml?topic=human-mouse-rat; Three-way gene-based synteny.

Publication types