North Carolina-based genetic resources fuel big scientific progress
|February 29, 2012|
A series of 15 scientific papers published this week placed North Carolina at the epicenter of a scientific resource called the Collaborative Cross – a “library” of genetic diversity that scientists believe can help fast-track important discoveries about genetics and disease into new discoveries, tests and treatments that impact human health. The articles appear in Genetics and G3: Genes|Genomes|Genetics, journals of the Genetics Society of America.
UNC Gillings School of Global Public Health biostatistics faculty members Fei Zou, PhD, associate professor, Wei Sun, PhD, assistant professor, and Fred Wright, PhD, professor, were involved in developing the project and in the design of breeding experiments based on the Collaborative Cross.
Researchers long have been frustrated by promising lab results that hit obstacles on the road to human application. Sometimes this is because research with other living organisms is limited in terms of conclusions scientists safely can extrapolate to the human population. Organisms studied in the laboratory lack the genetic diversity of humans.
To overcome this obstacle, scientists have begun to create libraries of genetic material. These libraries, called Genetic Resource Panels (GRPs), enable researchers to consider how genetic variation impacts living systems in a careful and systematic manner – an approach they think will help draw more robust conclusions, often more quickly.
The Collaborative Cross, a project aimed at mirroring the diversity of human genetics in the laboratory mouse population, is one such GRP. The Collaborative Cross contains ten times the genetic diversity of a typical laboratory mouse population — a level equivalent to the natural genetic variation in humans. Furthermore, the genetic diversity is spread out across the genome of the Collaborative Cross, while the limited ancestry of typical laboratory mice means that about half of the genome lacks good data for geneticists. The Collaborative Cross fills those gaps, and for scientists, the result is a fast track to understanding and testing new treatment and prevention approaches for numerous human diseases with an underlying genetic component.
Since the project’s beginning, Sun, Wright and Zou have worked actively on the design of the Collaborative Cross and on developing efficient statistical procedures.
“The Collaborative Cross will become a valuable resource to biomedical research communities and be applied to a large set of biological problems,” Zou says. “Biostatistics is essential to the success of the project, and to make sense of the data, rigorous analytic approaches are needed.”
Wright emphasized that biostatisticians are increasingly important in team science, especially with large genomics datasets, for which careful interpretation is necessary. “We are now involved in studies for which the data are so complex that a careful statistical analysis is necessary before even seeing the initial results,” he says.
The project is led by Fernando Pardo-Manuel de Villena, PhD, professor in the UNC School of Medicine’s Department of Genetics and member of UNC Lineberger Comprehensive Cancer Center, David Threadgill, PhD, a geneticist at North Carolina State University and UNC Lineberger member, and Gary Churchill, PhD, at The Jackson Laboratory. The mice are housed and ‘curated’ at UNC-Chapel Hill.
Pardo-Manuel de Villena is lead author on the paper featured on the cover of Genetics, which provides the first comprehensive description of the mouse genome library. The library is being shared with scientists across the country through an online resource called a genome browser.
“It is important that all scientists have free access to this resource, which is a census of every genetic line we have and consolidates the work of researchers in the U.S., Israel and Australia in one central place,” he says.
“Data sharing is particularly crucial for GRPs like the Collaborative Cross,” say the editors of Genetics and G3 in an editorial accompanying the papers. “If some pieces of the puzzle have been taken off the board … then the puzzle is unlikely to be completed and the community resource is compromised.”
The collaborative cross consortium includes scientists from the following institutions: Tel Aviv University; Geniad, Ltd., University of Western Australia, and Animal Resources Centre, Australia; Wellcome Trust Centre for Human Genetics, University of Oxford, University of North Carolina, Chapel Hill, North Carolina State University; The Jackson Laboratory; National Institutes of Health; Oregon Health and Science University; University of Arizona; University of Colorado Denver; University of Washington; Faculty of Dental Medicine, Hadassah Medical Centers and The Hebrew University, Jerusalem, University of Tennessee Health Science Center; Helmholtz Centre for Infection Research & University of Veterinary Medicine; Duke University; National Institute of Environmental Health Sciences, National Toxicology Program; University of Nebraska-Lincoln; University of Wisconsin-Madison; The Genome Institute at Washington University, St. Louis; and the University of Colorado School of Medicine.
The research was supported by grants from the National Institutes of Health, Ellison Medical Foundation, National Science Foundation, Australian Research Council and the Wellcome Trust. Essential support was provided by the Dean of the UNC School of Medicine, UNC Lineberger Comprehensive Cancer Center and the University Cancer Research Fund from the state of North Carolina. Tel-Aviv University provided core funding and technical support.