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

Genome Res. 2004 Apr;14(4):685-92. doi: 10.1101/gr.2067704.

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.

Publication types

  • Comparative Study
  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Automation*
  • Computational Biology / methods
  • Computational Biology / trends
  • Exons / genetics
  • Genome*
  • Genome, Human*
  • Humans
  • Mice
  • Physical Chromosome Mapping / methods
  • Physical Chromosome Mapping / trends
  • Rats
  • Sequence Alignment / methods*
  • Sequence Alignment / standards
  • Sequence Alignment / trends*
  • Software
  • Synteny / genetics