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/HlLtJ, 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size and minimizes the effects of drift and selection on allele frequencies in the DO (Rockman and Kruglyak 2008; unpublished simulations).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.
- Diversity Outbred Genotype Data2013High-precision genetic mapping of behavioral traits in the diversity outbred mouse population
Animal Models and Their Value in Predicting Drug Efficacy and Toxicity New York Academy of Sciences, New York, NY
IMGC 2014, Bar Harbor, ME, USA
CTC 2014, Berlin, Germany
Tongjun Gu, Robert E. Braun, Gary A. Churchill
Gordon Research Conference on RNA Editing, Galveston, TX
Genetically Diverse Mouse Models Workshop, ILSI Health and Environmental Sciences Institute, Washington, DC
40th Maine Biological and Medical Sciences Symposium, Bar Harbor, ME