JAX partners in international mouse sequencing project

JAX® NOTES Issue 513, Spring 2009

In 2000, the human genome sequence was completed. Just over two years later, the sequence of JAX® Mice strain C57BL/6J was published. Three years from now, the sequences of the 17 most widely used laboratory mouse strains (13 are JAX® Mice strains) will be completed — thanks to a $4.6 million, three-year project launched by the Welcome Trust Sanger Institute. The "Mouse Genomes Project" is a collaboration between the Sanger Institute, the MRC Mammalian Genetics Unit (Harwell), the MRC Human Genetics Unit (Edinburgh), the Wellcome Trust Centre for Human Genetics (Oxford), the European Bioinformatics Institute, and The Jackson Laboratory. It is being funded by the UK's Medical Research Council and the Juvenile Diabetes Research Foundation and is supported by an international scientific advisory board of leading mouse researchers. Scientists who use the sequenced strains will have to spend far less time identifying the genes within large loci associated with complex traits and be able to spend more time understanding the genes' biological mechanisms.

  • 129P2
  • 129S1/SvImJ 
  • 129S5
  • A/J
  • AKR/J
  • BALB/cJ
  • C3H/HeJ
  • C57BL/6N 
  • CAST/EiJ
  • CAST/EiJ
  • CBA/J
  • DBA/2J
  • LP/J
  • NOD/ShiLtJ
  • NZO
  • PWK/PhJ
  • Spretus/EiJ
  • WSB/EiJ

Although thousands of genetically defined mouse strains are available to the scientific community, most researchers use the much smaller subset of 17 strains that the Sanger Team will sequence. JAX Professor Gary Churchill helped the team select those strains. In particular, he recommended including some of the eight genetically diverse founder strains for the collaborative cross.

To sequence the 17 strains, the Sanger Team will use Illumina's Genome Analyzer. In the first 18 months, the team will produce draft sequences of the 17 strains and, to maximize the benefits of its work, will freely release the drafts to the research community through the Ensembl genome browser. Over the final 12 months, the team will produce final sequence drafts. As a pilot project, the team has already sequenced a region of mouse chromosome 17 that contains many of the genes involved in the immune system. Dr. David Adams, project leader and investigator at the Wellcome Trust Sanger Institute, says the results so far indicate that the researchers are "doing an extremely good job" at calling SNPs and small indels. However, "how well we do with some of the complex repeats and the copy number variants is something we are still working on."

Ultimately, the sequences will help researchers better understand and treat human disease. Mouse strains differ from each other in a wide range of medically important characteristics, and these differences are a result of complex genetic variations between them. The Sanger Project will reveal these variations. As in humans, genetic variations produce different phenotypes, some of which mirror human diseases, such as heart disease, diabetes, and cancer. As Dr. Adams says, "By sequencing the background strains, we can uncover that diversity and use that as the basis to finding disease genes and disease pathways."

References

In Sequence. 2008. Sanger Institute to sequence 17 mouse strains on Illumina's GA, attempt de novo assembly. Dec. 16 press release.

The Jackson Laboratory. 2008. The Jackson Laboratory partnering in international mouse sequencing project. Dec. 17 press release.