Churchill and Fernando Pardo-Manuel de Villena, Ph.D., of the University of North Carolina, Chapel Hill, leading an international research team, created a genome-wide, high-resolution map of most of the inbred mouse strains used today. Their conclusion, published in Nature Genetics: Most of the mice in use today represent only limited genetic diversity, which could be significantly expanded with the addition of more wild mouse populations.
The current array of laboratory mouse strains is the result of more than 100 years of selective breeding. In the early 20th century, America's first mammalian geneticists, including Jackson Laboratory founder Clarence Cook Little, sought to understand the genetic processes that lead to cancer and other diseases. Mice were the natural experimental choice as they breed quickly and prolifically and are small and easy to keep.
Lacking the tools of molecular genetics, those early scientists started by tracking the inheritance of physical traits such as coat color. A valuable source of diverse-looking mouse populations were breeders of "fancy mice," a popular hobby in Victorian and Edwardian England and America as well as for centuries in Asia.
In their paper, Churchill and Pardo-Manuel de Villena report that "classical laboratory strains are derived from a few fancy mice with limited haplotype diversity." In contrast, strains that were derived from wild-caught mice "represent a deep reservoir of genetic diversity," they write.
The team created an online tool, the Mouse Phylogeny Viewer, for the research community to access complete genomic data on 162 mouse strains. "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.
"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.
Churchill and Pardo-Manuel de Villena have been working for almost a decade with collaborators around the world to expand the genetic diversity of the laboratory mouse. In 2004 they 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."
Other team members include Hyuna Yang, Ph.D., from The Jackson Laboratory; Leonard McMillan, Ph.D., two graduate students Jeremy Wang and Catherine Welsh from the UNC-Chapel Hill Department of Computer Science; Timothy Bell, Ryan Buus and graduate student John Didion from the UNC-Chapel Hill Department of Genetics, UNC Lineberger and the Carolina Center for Genome Sciences; Francois Bonhomme, Ph.D., and Pierre Boursot, Ph.D., from the Université Montpellier (France); Alex Yu, Ph.D., from the National Taiwan University; Michael Nachman, Ph.D., from the University of Arizona; Jaroslav Pialek, Ph.D., from the Academy of Sciences of the Czech Republic, and Priscilla Tucker, Ph.D., from the University of Michigan.
The research was supported by the National Institute of General Medical Sciences (part of the National Institutes of Health), and several additional National Institutes of Health grants, a Czech Science Foundation grant and a University of North Carolina Bioinformatics and Computational Biology training grant.
Yang et al.: Subspecific origin and haplotype diversity in the laboratory mouse. Nature Genetics, advance online publication Sunday, May 29, 2011, http://dx.doi.org/10.1038/847.
Joyce Peterson | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences