The Collaborative Cross (CC)
Partly conceived and developed by Dr. Gary Churchill, The Collaborative Cross (CC) is a large panel of new inbred mouse strains that are currently being developed through a community effort. The CC was designed to address some of the perceived shortcoming of available mouse strain resources, including small numbers of strains, limited genetic diversity, and a complex history that results in unknown confounding relationships among common inbred strains.
The CC strains are derived from an eight way cross using a set of founder strains that include three wild-derived strains: A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HiLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ.
The wild strains contribute 75% of the genetic diversity of the CC. Without relevant genetic diversity, forward genetic approaches cannot make discoveries. The CC captures a substantial proportion of the genetic diversity available in laboratory mouse strains, estimated to be roughly twice the number of common SNPs in the human population (Yang et al., 2007). This diversity is approximately 4 times that in the widely used “classical” inbred strains.
The CC will provide a common reference panel specifically designed for the integrative analysis of complex systems. It will be a genetically defined panel and, as all the strains are fully reproducable, genotyping need only be done once.
Papers and Datasets
Aylor DL, Valdar W, Foulds-Mathes W, Buus RJ, Verdugo RA, Baric RS, Ferris MT, Frelinger JA, Heise M, Frieman MB, Gralinski LE, Bell TA, Didion JD, Hua K, Nehrenberg DL, Powell CL, Steigerwalt J, Xie Y, Kelada SN, Collins FS, Yang IV, Schwartz DA, Branstetter LA, Chesler EJ, Miller DR, Spence J, Liu EY, McMillan L, Sarkar A, Wang J, Wang W, Zhang Q, Broman KW, Korstanje R, Durrant C, Mott R, Iraqi FA, Pomp D, Threadgill D, Pardo-Manuel de Villena F, Churchill GA.
Genetic analysis of complex traits in the emerging collaborative cross
Genome Res. 2011 Aug;21(8):1223-38. PMCID: PMC3149489 [ Full Text ] [ datasets ]
Chesler EJ, Miller DR, Branstetter LR, Galloway LD, Jackson BL, Philip VM, Voy BH, Culiat CT, Threadgill DW, Williams RW, Churchill GA, Johnson DK, Manly KF.
The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics
Mamm Genome. 2008 Jun;19(6):382-9. PMCID: PMC2745091 [ Full Text ]
Collaborative Cross Consortium
The Genome Architecture of the Collaborative Cross Mouse Genetic Reference Population
Genetics. 2012 Feb;190(2):389-401. PMCID: PMC3276630 [ Full Text ] [ datasets ]
Complex Trait Consortium.
The Collaborative Cross, a community resource for the genetic analysis of complex traits
Nat Genet. 2004 Nov;36(11):1133-7.
The Collaborative Cross, developing a resource for mammalian systems genetics: a status report of the Wellcome Trust cohort
Iraqi FA, Churchill G, Mott R.
Mamm Genome. 2008 Jun;19(6):379-81.
Kelada SNP, Aylor DL, Peck BCE, Ryan JF, Tavarez U, Buus RJ, Miller DR, Chesler EJ, Threadgill DW, Churchill GA, Pardo-Manuel de Villena F, Collins FS.
Genetic Analysis of Hematologic Parameters in Incipient Lines of the Collaborative Cross
G3 (Bethesda). 2012 Feb;2(2):157-65. PMCID: PMC3284323 [ Full Text ] [ datasets ]
Lenarcic AB, Svenson KL, Churchill GA, Valdar W.
A General Bayesian Approach to Analyzing Diallel Crosses of Inbred Strains
Genetics. 2012 Feb;190(2):413-35. PMCID: PMC3276624 [ Full Text ] [ datasets ] [ software ]
Mathes WF, Aylor DL, Miller DR, Churchill GA, Chesler EJ, de Villena FP, Threadgill DW, Pomp D.
Architecture of energy balance traits in emerging lines of the Collaborative Cross
Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1124-34. PMCID: PMC3118585 [ Full Text ] [ datasets ]
Philip VM, Sokoloff G, Ackert-Bicknell CL, Striz M, Branstetter L, Beckmann MA, Spence JS, Jackson BL, Galloway LD, Barker P, Wymore AM, Hunsicker PR, Durtschi DC, Shaw GS, Shinpock S, Manly KF, Miller DR, Donohue KD, Culiat CT, Churchill GA, Lariviere WR, Palmer AA, O'Hara BF, Voy BH, Chesler EJ.
Genetic analysis in the Collaborative Cross breeding population
Genome Res. 2011 Aug;21(8):1223-38. PMCID: PMC3149490 [ Full Text ] [ datasets ]
Threadgill DW, Pardo-Manuel de Villena F, Miller DR, Miller DR, Churchill GA.
The collaborative cross: a recombinant inbred mouse population for the systems genetic era
ILAR J. 2011 Feb 8;52(1):24-31. [ Full Text ]
A new mouse collaborative cross resource promises new cures and treatments for diseases
Feb 16, 2012. A new genetic resource from an international research consortium is expected to accelerate the development of new cures and treatments for a wide range of human diseases. This project, called the mouse "Collaborative Cross" (CC) resource, will increase the likelihood that experiments conducted in mice will advance our understanding of human biology. The mice in the CC have 90 percent of the genetic diversity present in laboratory mice, which mirrors the genetic diversity in humans. This will enable researchers to study traits and human diseases of complex origins in an appropriate model system. Read the special issues of Genetics and G3: Genes|Genomes|Genetics.
How to build a better mouse
July 19, 2011. The Collaborative Cross project will boost diversity and help the hunt for disease genes.
Nature News article highlights the Collobrative Cross project. [ Full Text ]
Collaborative Cross Paper Highlighted in Nature Reviews Genetics
April 18, 2011. Complex traits: Mice line up for success. Recombinant inbred lines (RILs), which are generated by crossing individuals with polymorphic genotypes followed by several generations of inbreeding, are valuable resources for studying the genetic basis of complex traits. Given the track record of mice for improving our understanding of human disease, there is great hope for what could be achieved with the extensive panel ofmouse RILs that is being developed in the Collaborative Cross (CC). The first experiments with partially inbred CC lines (pre-CC lines) have now been reported and demonstrate the power of this emerging genetic resource. [ Highlight in Nature Reviews Genetics ] [ Full Text of Paper ]
Engineered Mice Mimic Human Populations
February 5, 2010. Research Triangle Park, N.C.—The mice are pretty odd. Distributed among 2,000 cages, they represent a real hodgepodge: white, black and brown mice, some fat, some skinny, some with crooked tails, some huddling in corners while others scamper in circles. These mice from the University of North Carolina at Chapel Hill, awaiting a new housing facility here, aren’t mutant rejects. Instead they are a valuable new resource—the most diverse mouse strains to ever hit the lab bench. Because they more closely reflect the genetic variation of humans, they may be the key to understanding some of today’s most common, and most complex, diseases.
Collaborative Cross to improve systems genetics analysis
Spring 2009. JAX Professor Gary Churchill helped design the Collaborative Cross. Genetic analysis is experiencing a new dawn — systems genetics, the study of the interactions among the genes in a biochemical pathway. A relatively new concept, systems genetics will help scientists better understand how genes function in the context of the entire biochemical pathway to which they belong. To realize the potential of systems genetics, researchers conducting mouse-based biomedical research will need new tools — tools that will allow them to better resolve Quantitative Trait Loci (QTL) intervals and identify the underlying genes. The Collaborative Cross (CC) promises to be such a tool.