Research Team Maps Lab Mouse Genome

Sharing about 95 percent of their genes with humans, mice are recognized around the world as the leading experimental model for studying human biology and disease. But, says Jackson Laboratory Professor Gary Churchill, Ph.D., researchers can learn even more “now that we really know what a laboratory mouse is, genetically speaking.”

Thanks to an in-depth analysis by a team led by Fernando Pardo-Manuel de Villena, PhD, in the University of North Carolina, Chapel Hill Department of Genetics and Gary Churchill, PhD, at The Jackson Laboratory in Bar Harbor, Maine, researchers will be able to use an online resource dubbed the Mouse Phylogeny Viewer to select from among 162 strains of laboratory mice for which the entire genome has been characterized.

Phylogeny is the connections among all groups of organisms as understood by genetic relationships. The results of the analysis that make this tool possible were published online today in the journal Nature Genetics.

“The viewer provides scientists with a visual tool where they can actually go and look at the genome of the mouse strains they are using or considering, compare the differences and similarities between strains and select the ones most likely to provide the basis for experimental results that can be more effectively extrapolated to the diverse human population,” explains Pardo-Manuel de Villena.

“As scientists use this resource to find ways to prevent and treat the genetic changes that cause cancer, heart disease, and a host of other ailments, the diversity of our lab experiments should be much easier to translate to humans,” he noted.

In 2004 Churchill and Pardo-Manuel de Villena launched the Collaborative Cross, a project to interbreed eight different strains--five of the classic inbred strains and three wild-derived strains. In 2009 Churchill’s lab started the Diversity Outbred mouse population with breeding stock selected from the Collaborative Cross project.

The research team estimates that the standard laboratory mouse strains carry about 12 million single nucleotide polymorphisms (SNPs), single-letter variations in the A, C, G or T bases of DNA.

The Collaborative Cross mice deliver a whopping 45 million SNPs, as much as four times the genetic variation in the human population. “All these variants give us a lot more handles into understanding the genome,” Churchill says.

“This work creates a remarkable foundation for understanding the genetics of the laboratory mouse, a critical model for studying human health,” said James Anderson, Ph.D., who oversees bioinformatics grants at the National Institutes of Health.

“Knowledge of the ancestry of the many strains of this invaluable model vertebrate will not only inform future experimentation but will allow a retrospective analysis of the huge amounts of data already collected,” he concluded.

Their analysis exponentially increases the data available to geneticists who work with mice, allowing them to statistically impute the whole mouse genome sequence with very high accuracy for hundreds of laboratory mouse strains. This will lead to much greater precision in the interpretation of existing biomedical data and optimal selection of strains in future experiments.