An international team of researchers, including University of Wisconsin-Madison geneticist Bret Payseur, describe in the Sept. 14 issue of the journal Nature the genome sequencing and comparison of 17 mouse strains, including several of the most common laboratory strains and four recently derived from wild populations. The resulting database, the largest for any vertebrate model organism, documents the range of genetic variation between mouse strains and its effects on phenotypes and gene regulation.
"Mice are the premier model organism for human disease. We've made a lot of progress in understanding the genetics of common human diseases by studying mice," says Payseur, an associate professor of medical genetics in the UW-Madison School of Medicine and Public Health. "Although we've been able to map genomic regions that contribute to disease risk, we haven't known the full spectrum of mutations involved."
The new genetic compendium will help researchers more quickly find the subset of sequence differences responsible for disease and other characters, he adds. The new paper identifies mutations associated with more than 700 biological traits, including diabetes and heart disease.
"We are living in an era where we have thousands of human genomes at our fingertips," says David Adams from the Wellcome Trust Sanger Institute, who led the project. "The mouse, and the genome sequences we have generated, will play a critical role in understanding of how genetic variation contributes to disease and will lead us towards new therapies."
In addition to advancing the use of mice as a model for human disease, Payseur says the work also advances studies of evolution, his key interest. "We were interested in the history of mice — how did mice evolve and come to be such an important organism for research?" he asks.
He and graduate student Michael White probed the evolutionary history of the lab mouse using sequences of four wild-derived mouse strains, including three common subspecies of house mice and a more distant relative. These strains represent a few million years of evolution, offering a window into the processes that drive genetic and phenotypic change.
They found that the mouse genomes do not reflect a single evolutionary story. Rather, different parts of the genome showed different patterns of relatedness. For the three wild house mouse subspecies in this study, Payseur and White found that nearly 40 percent of the sequence supported one evolutionary relationship, another 30 percent supported another and the remaining 30 percent of the DNA suggested yet a third relationship.
The complexity uncovered here should serve as a cautionary tale for studies of evolutionary relationships between organisms, which have often made inferences based on one or a few genes, Payseur says. "If you're looking at closely related species, don't expect to infer the species history just by looking at a handful of regions. You really have to look at a large fraction of the whole genome."
Payseur hopes to conduct similar analyses of the other sequenced laboratory strains to begin to fill in the large gaps in existing lab mouse pedigrees. Understanding the evolution of the lab mouse will provide important genetic context for mouse studies of human disease and help other researchers choose the strain most appropriate for their research questions.
This genomic-sequencing project was supported by The Medical Research Council, U.K., and the Wellcome Trust. Payseur's work was supported by the U.S. National Science Foundation.
Bret Payseur | EurekAlert!
The birth of a new protein
20.10.2017 | University of Arizona
Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
20.10.2017 | Information Technology
20.10.2017 | Materials Sciences
20.10.2017 | Interdisciplinary Research