Taking stock of the Collaborative Cross

Five years ago, the journals Genetics and G3 published a series of papers that reported the first data from the genetic resource population known as the Collaborative Cross. This week, two journals release special issues highlighting the breadth of work this tool has made possible.

Taking stock of the Collaborative Cross click to enlarge Fernando Pardo Manuel de Villena, PhD

Media contact: Matt Englund, (919) 923-2347, matthew.englund@unchealth.unc.edu

June 7, 2017

CHAPEL HILL, NC – This week the journals Genetics and G3 will both release special issues on multiparental populations (MPP), in particular focusing on the wide impact of the Collaborative Cross (CC). The CC is a multiparental inbred mouse population that serves as an important experimental tool for genetic researchers and is housed and administered by UNC’s Department of Genetics.

Of the 14 papers collectively released by both journals, six feature UNC researchers as co-authors. The diversity of approaches reported in the journals speaks to the experimental power of the CC. The results reported in these papers include the release of whole genome sequences of 69 CC strains.

“Quantitatively, this is a very significant leap,” said Fernando Pardo Manuel de Villena, PhD, interim chair of genetics and co-author of several of the papers.  

Just a few years ago, only 17 whole mouse genomes were available. The findings released this week will more than quadruple the amount of data available about mouse genomes.

”The genomes of the 69 strains will be made available through a number of resources and databases, making them searchable for the research community,” said Pardo Manuel de Villena. “This will be an invaluable resource for researchers working to design experiments or interpret results.”

Through this resource, researchers will be able to directly search the sequenced genomes, an advance that will greatly enhance the CC as a resource for both genetic mapping and disease model development.

Part of the CC’s power lay in the diversity of its population, which allows researchers to assess the role of genetic variation in a wide spectrum of medically relevant phenotypes – observable physical and biochemical characteristics and traits of an organism. This variation makes the CC an excellent tool for disease modeling. For example, in 2014, the CC population was used to replicate the full spectrum of human responses to Ebola virus infection, providing the research community with an important tool in the fight against that deadly disease.  

 CC mice are also inbred, which means that though they are genetically diverse across strains, the genomes of mice within the same strain are identical. This allows for experimental reproducibility that is theoretically infinite.

Other highlights of the UNC-authored research include genetic and molecular characterization of a number of biomedically important traits, such as infertility and responses to viral infections.

“These papers really complement each other” said Martin Ferris, PhD, assistant professor in the department of genetics and co-author on several of these papers. “We were able to discover sets of genes driving severe disease following either SARS or West Nile virus infection, and then leverage the new CC genetic information from that study to inform us as to what exact genetic differences were causing severe responses to infection.”

Shortly after the CC became a publicly available resource in 2012, Genetics released a special issue, spearheaded by Pardo Manuel de Villena, on the genetics resource. The paper in that issue describing the CC became one of the most cited articles in Genetics.

The Genetics and G3 special issues released this week revisit this topic in order to report on how the resource is being used and what new advancements can be shared across multiparental populations.

In addition to the research papers, the issues will also include a commentary from two editors of Genetics, Dirk-Jan de Koning and Lauren M. McIntyre, as well as a young researcher profile on Andrew Morgan, an MD/PhD student in Pardo Manuel de Villena’s lab and co-author of several of the papers.  

As for what’s next for the CC, Pardo Manuel de Villena said that it’s up to the researchers themselves. “This is a resource. How it’s used depends on the ingenuity of the research community. It’s like a microscope; what you choose to examine is up to you.”

Pardo Manuel de Villena also said that it’s up to researchers to begin planning now for the kind of resources that they will need in 20 years

“If we don’t start building them, they are not going to be available. The first meetings about the CC were in 2001. It took three years after that to get the project started and the first data wasn’t released until 2012. It’s just now in 2017 that things are starting to come to fruition. That’s the time frame it takes for a project like this – is there something we need to be doing now that can make something better than the CC in the future?”

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