Mapping the Mouse Genome

An international research consortium that includes TIGR has published a comprehensive physical map of the mouse genome that provides an important resource for biomedical researchers. The TIGR team, led by Shaying Zhao, sequenced the BAC ends of the mouse genome.

August 5, 2002

An international consortium that includes The Institute for Genomic Research (TIGR) has developed the most comprehensive physical map so far of the mouse genome, an important resource for identifying both mouse and human genes.

The consortium, whose work was coordinated by the Wellcome Trust Sanger Institute in the United Kingdom, published its physical map of the mouse genome - which covers about 98% of the mouse DNA sequence - in Nature online on August 4th.

The two-year research project involved sequencing centers and labs in Britain, the United States, and Canada. Scientists successfully overlapped more than 300,000 mouse genomic DNA fragments and used other mouse chromosome data in building a physical map that has fewer than 300 gaps.

TIGR's role in the project was sequencing what are known as "BAC end sequences" (or "BAC ends") of the mouse genome. That helped scientists draw the new genome map by anchoring mouse DNA fragments to specific sites in the human genome.

BACs (bacterial artificial chromosomes) are large fragments of an organism's DNA that can replicate inside a bacterial cell. A "BAC Library" - a collection of segments of an organism's genome - can be pieced together to create a map of the whole genome. That map then provides a framework for assembling data from "whole genome shotgun" sequencing of the same organism's genome.

TIGR, which has been conducting large-scale BAC end sequencing since 1997, has built the sequencing and bioinformatics infrastructure to carry out such sequencing at the highest level of accuracy. And scientists say that BAC ends were extremely important for developing the map of the mouse genome

"BAC ends anchor the mouse genome fragments to parallel sites in the already-sequenced human genome - a critical step in construction the mouse map," said Shaying Zhao, an assistant investigator who led the mouse BAC end sequencing project at TIGR. Since she joined TIGR as a postdoctoral fellow in 1998, Zhao has led TIGR's large-scale BAC end sequencing of mammals that include the mouse, rat, and human genomes.

Zhao said, "BAC ends provide highly specific sequence markers across the genome. No matter what strategy is chosen to sequence a large genome - either whole genome shotgun, 'BAC to BAC,' or a combination of both techniques - BAC ends are an essential resource required to map and sequence the genome."

An accurate genome map of the mouse is important to biomedical researchers who use DNA sequence information for their research. Because the mouse genome is a vital tool for understanding the human genome sequence, detailed comparisons can highlight important parts of the sequence. For example, "control regions" -- because they act to control genes -- are key to understanding the genes' role in health and disease.

Simon Gregory, leader of the mouse project at Sanger, called the new physical map "an exceptional resource that covers almost 100% of the mouse genome. The map allows us to pick out the regions that are lacking in the whole genome assembly, to focus on genes and to highlight regions of similiarity between mouse and human."

Aside from the Wellcome Trust Sanger Institute and TIGR, the other research centers that contributed to the mouse project were: the Washington University School of Medicine Genome Sequencing Center and its Department of Electrical Engineering, in St. Louis; the British Columbia Cancer Agency's Genome Sciences Center, in Vancouver, British Columbia; the Children's Hospital Oakland Research Institute, in Oakland, Cal.; and the European Bioinformatics Institute, in Hinxton, U.K.