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You are here: Home / News / 2011 News / Of Mice and Men: UNC-led team solves mouse genome dilemma

Of Mice and Men: UNC-led team solves mouse genome dilemma

by Mary Ruth last modified May 29, 2011 03:47 PM
Data will help scientists worldwide design better experiments.

Chapel Hill, NC – Laboratory research has always been limited in terms of what conclusions scientists can safely extrapolate from animal experiments to the human population as a whole.  Many promising findings in mice have not held up under further experimentation, in part because laboratory animals, bred from a limited genetic foundation, don’t provide a good representation of how genetic diversity manifests in the broader human population.

Now, thanks to an in-depth analysis by a team led by Fernando Pardo-Manuel de Villena, PhDIcon indicating that a link will open an external site., in the UNC Department of GeneticsIcon indicating that a link will open an external site. and Gary Churchill, PhDIcon indicating that a link will open an external site., at The Jackson LaboratoryIcon indicating that a link will open an external site. in Bar Harbor, Maine, researchers will be able to use an online resource dubbed the Mouse Phylogeny ViewerIcon indicating that a link will open an external site. to select from among 162 strains of laboratory mice for which the entire genome has been characterized.  Phylogeny refers to the connections among all groups of organisms as understood by ancestor/descendant relationships.  Pardo-Manuel de Villena is also a member of UNC Lineberger Comprehensive Cancer Center and the Carolina Center for Genome SciencesIcon indicating that a link will open an external site..

The results of the analysis that make this tool possible were published online today in the journal Nature GeneticsIcon indicating that a link will open an external site..

“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,” said Pardo-Manuel de Villena.

Mouse Genome“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.

He explains that the DNA of a given pair of typical laboratory mouse strains varies in only half of their genome and captures less than 20 percent of the diversity of the entire mouse genome.  Historically, biomedical researchers have relied on what are called classical inbred strains of mice in laboratory research.  With the advance of genetic science, researchers began to use wild-derived laboratory strains (descendants of captured wild mice that originate from a small number of original ancestors) to try to overcome issues associated with limited genetic diversity.  However, scientists’ understanding of genetic diversity in mice has – until now – been limited and biased toward the most frequently used strains.

The team compared the genome of a large and diverse sample including 36 strains of wild-caught mice, 62 wild-derived laboratory strains and 100 classical strains obtained from different stocks and different laboratories using the Mouse Diversity array – a technology that maps the entire mouse genome.

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 – leading to much greater precision in the interpretation of existing biomedical data and optimal selection of strains in future experiments.

The Mouse Phylogeny Viewer is available at http://msub.csbio.unc.edu/Icon indicating that a link will open an external site..

Other team members include Leonard McMillan, PhD, two graduate students Jeremy Wang and Catherine Welsh from the UNC-Chapel Hill Department of Computer ScienceIcon indicating that a link will open an external site.; Timothy Bell, Ryan Buus and graduate student John Didion all from the UNC-Chapel Hill Department of Genetics Icon indicating that a link will open an external site., UNC Lineberger and the Carolina Center for Genome SciencesIcon indicating that a link will open an external site.; Hyuna Yang, PhD, from The Jackson LaboratoryIcon indicating that a link will open an external site.; Francois Bonhomme, PhD, and Pierre Boursot, PhD, from the Universite Montpellier (France) Icon indicating that a link will open an external site.; Alex Yu, PhD, from the National Taiwan UniversityIcon indicating that a link will open an external site.; Michael Nachman, PhD , from the University of ArizonaIcon indicating that a link will open an external site.; Jaroslav Pialek, PhD, from the Academy of Sciences of the Czech RepublicIcon indicating that a link will open an external site., and Priscilla Tucker, PhD, from the University of MichiganIcon indicating that a link will open an external site..

The research was supported by the National Institute of General Medical Sciences Icon indicating that a link will open an external site.(part of the National Institutes of HealthIcon indicating that a link will open an external site.), and several additional National Institutes of HealthIcon indicating that a link will open an external site. grants, a Czech Science FoundationIcon indicating that a link will open an external site. grant and a University of North Carolina Bioinformatics and Computational BiologyIcon indicating that a link will open an external site. training grant.