The public-domain effort to sequence the mouse genome is set to accelerate, following the completion of a physical map of the genome.

Points of reference: work on the mouse genome is helping to fill gaps in the human genome sequence. Credit: SIMON GREGORY, RICHARD SUMMERS AND THE ENSEMBL TEAM

Sequence data flowing from the international Mouse Sequencing Consortium can now be anchored to the map, speeding up assembly of the complete genome. The project is the first to use human-genome data as a framework to build a map of another genome, and provides a proof-of-principle that will speed up completion of the genomes of other species.

The map, which offers a complete tiling path for each chromosome, is available at the Ensembl database (see below). In it, the 290,000 bacterial clones in the sequence have been assembled into just 554 contiguous blocks, or contigs, spanning 3,080 megabases — 98% of the entire mouse genome. This relatively small number of contigs will make it easy to assemble the full genome, researchers say.

The low number of contigs and the speed with which the map has been completed can be attributed to the usefulness of the human genome sequence as a guide, say members of the multicentre team that created the map. Mouse genes align well with human ones, and long blocks of the sequence are common to both genomes. The team used information from these common blocks to help them place and orientate the mouse-clone contigs; this enabled them to reduce the number of contigs from more than 7,000.

In turn, the mouse map is also helping to plug remaining gaps in the human genome sequence. By aligning the mouse map next to the human sequence, mouse contigs have already been identified as spanning gaps in the human genome.

The availability of the mouse map means that assembly of the entire mouse genome can proceed apace. The Mouse Sequencing Consortium is generating sequence by applying the high-throughput 'shotgun' sequencing method pioneered by Celera Genomics of Rockville, Maryland, using some 6 million fragments between 500 and 700 bases long (see Nature 411, 121; 2001).

“We can now nail the emerging mouse assemblies to the map,” says Tim Hubbard of the Sanger Centre near Cambridge in England. Hubbard expects to have produced a rough first bash at the entire genome within the next few weeks, with continual refinement over the coming months.

The map was generated by groups at the Sanger Centre; the Genome Sequence Centre in British Columbia, Canada; Washington University in St Louis, Missouri; and the Institute for Genomic Research in Rockville, Maryland.

→ http://mouse.ensembl.org