Mouse Gene Map Published Online

Applied Genetics News,  August, 2002  

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An international consortium, whose work was coordinated by the Wellcome Trust Sanger Institute (Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, U.K.; Tel: +44 (0)1223-834244, Fax: +44 (0)1223 494919; Website: www.sanger.ac.uk), has developed the most comprehensive physical map so far of the mouse genome. The consortium, in the United Kingdom, published its physical map of the mouse genome-which covers approx. 98% of the mouse DNA sequence-in Nature online on August 4.

The 2-yr research project involved sequencing centers and labs in Britain, the United States, and Canada. The physical map contains 296 contigs of overlapping bacterial clones and provides a framework to assemble the whole genome-shotgun sequence data for the organism. The clone map still has 275 gaps, however. To align the mouse contigs, the team used 51,486 human-mouse homology matches based on human and mouse sequences.

"A lot of genes in the human we don't have a function for them. If we are able to map them in a model organism like the mouse, we can derive their function by knocking them out," says study coauthor Simon Gregory of the Sanger Institute.

The Institute for Genomic Research (9712 Medical Center Dr., Rockville, MD 20850; Tel: 301/838-0200, Fax: 301/838-0208; Website: www.tigr.org) sequenced what are known as "BAC end sequences" (or "BAC ends") of the mouse 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.

"BAC ends anchor the mouse genome fragments to parallel sites in the already-sequenced human genome-a critical step in construction the mouse map," says Shaying Zhao, an assistant investigator who led the mouse BAC end sequencing project at TIGR.

The DNA-sequence information used to compile the physical map was gathered differently from the information used to compile the previously released draft sequence. Because the physical map comes from a separate source of genetic information, the researchers are using it to confirm the accuracy of the draft sequence.

"We are comparing the two independent data sets to be certain they are giving us the same answer," says John D. McPherson, from Genome Sequencing Center at Washington University School of Medicine in St. Louis (660 Euclid Ave., No. 8057, St. Louis, MO; Tel: 314/362-3567), which played a major role in the effort.

The physical map was assembled using longer segments of DNA than those used to assemble the draft sequence. The long segments were cloned in bacteria. Now that the mapping is complete, the bacteria containing these bits of mouse genome continue to be grown, stored in freezers, and carefully cataloged. Investigators studying mouse genes or regions of DNA now can locate the location of that particular segment on the map and obtain the actual clone of that region to study, rather than isolating the region themselves.

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