The Diversity Outbred (DO)
The Diversity Outbred (DO) is a heterogeneous stock derived from the same eight founder strains as the Collaborative Cross (CC) inbred strains: A/J, C57BL/6J, 129S1/SvImJ, NOD/ShiLtJ, NZO/HiLtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ.
In 2009, animals representing 144 independent lineages from the CC breeding colony at The Oak Ridge National Laboratory (Chesler et al. 2008) were used to seed the DO population, which was then maintained as a randomized breeding colony with a population size of 175 pairs.
One female and one male from each first litter are randomly assigned to a new breeding pair to make the next generation. This mating scheme doubles the effective population size and minimizes the effects of drift and selection on allele frequencies in the DO (Rockman and Kruglyak 2008; unpublished simulations). Each DO mouse is a unique individual with a high level of allelic heterozygosity, and the DO population provides an effectively unlimited source of novel allelic combinations.
The CC strains are being inbred to produce stable clones. The DO mice, on the other hand, are being maintained as an outbred stock. Advantages of outbreeding include, normal levels of heterozygosity, similar to the human genetic condition, and substantially increased mapping resolution. A drawback of the DO is that each animal is genetically unique and thus not reproducible. Combinations of genetic loci that are discovered in the DO mice can be replicated in CC strains or in their reproducible F1 progeny. In this regard, the CC and DO populations are complementary. Together these new resources will revolutionize our understanding, treatment and ultimately, prevention of pervasive human diseases.
DO Genotype Data
These directories contain all of the MUGA and MegaMUGA data that we have received. For each platform, we provide the raw genotype files generated by the genotyping facility and DO genome reconstructions as produced by DOQTL
DOQTL: An R package for the analysis of DO mice (beta-release).
DOQTL is an analysis pipeline that may be used to perform linkage and association mapping in DO mice as well as other multi-parent advanced generation intercross (MAGIC) populations. DOQTL uses genotyping array data to reconstruct DO genomes in terms of founder haplotypes. It performs linkage mapping using the haplotype reconstructions and can impute the founder variants onto DO genomes to perform association mapping.
Papers and Datasets
Munger SC, Churchill GA, Chesler EJ, Raghupathy N, Choi K, Simons AK, Gatti DM, Hinerfeld DA, Svenson KL, Keller MP, Attie AD, Hibbs MA, Graber JH
RNA-Seq Alignment to Individualized Genomes Improves Transcript Abundance Estimates in Multiparent Populations
Genetics 2014 Sep;198(1):59-73. PMID: 25236449. [ Seqnature Github site ] [ Simulation Data ] [ GEO Record ]
Daniel M. Gatti, Karen L. Svenson, Andrey Shabalin, Long-Yang Wu, William Valdar, Petr Simecek, Neal Goodwin, Riyan Cheng, Daniel Pomp, Abraham Palmer, Elissa J. Chesler, Karl W. Broman, Gary A. Churchill
Quantitative Trait Locus Mapping Methods for Diversity Outbred Mice
G3 (Bethesda). 2014 Sep 18;4(9):1623-33. doi: 10.1534/g3.114.013748. [ datasets ]
Svenson KL, Gatti DM, Valdar W, Welsh CE, Cheng R, Chesler EJ, Palmer AA, McMillan L, Churchill GA.
High-Resolution Genetic Mapping Using the Mouse Diversity Outbred Population
Genetics. 2012 Feb;190(2):437-47. PMCID: PMC3276626 [ Full Text ] [ datasets ]
IMGC 2014, Bar Harbor, ME, USA, October 28, 2014
CTC 2014, Berlin, Germany, May 19, 2014
Tongjun Gu, Robert E. Braun, Gary A. Churchill
Gordon Research Conference on RNA Editing, Galveston, TX, Jan 6-11, 2013. Poster
40th Maine Biological and Medical Sciences Symposium, Bar Harbor, ME, April 12-13, 2013. Talk
Genetically Diverse Mouse Models Workshop, ILSI Health and Environmental Sciences Institute, Washington, DC, November 28, 2012. Talk
Developing the Laboratory Mouse as a Tool for Systems Genetics (Video on meeting website)
Animal Models and Their Value in Predicting Drug Efficacy and Toxicity
New York Academy of Sciences, New York, NY, September 15-16, 2011. Talk
Diversity Outbred and Collaborative Cross Mice to Offer Maximum Allelic Variation
Summer 2009. In its quest to provide even more powerful genetically distinct mouse resources, JAX is developing a population of Diversity Outbred (DO) mice, designed to maximize allelic variation throughout the genome. Each DO mouse will be genetically unique, and groups of them will approximate the genetic diversity found in human populations.