Genetics and Genomics in Advanced Mouse Populations
Genetic reference populations are panels of isogenic lines that are produced and distributed as panels of clones. These resources are becoming an increasingly important resource for genetic analysis, particularly for the simultaneous integration of genetic variation with sequelae from molecular to whole organism variation. The widespread deployment of these populations motivated a systematic comparison of the structure of each, and its impact on the utility of the population for genetic mapping and genetic correlation analyses. Further, the construction of these populations is in itself an interesting biological experiment in the interactions of diverse genomes and the resulting random and non-random selection processes manifest after generations of outcrossing and inbreeding. We have performed an evaluation and comparison of genetic reference populations including common inbred strains, two progenitor recombinant inbred (RI) panels, and the emerging Collaborative Cross based on the development of linkage disequilibrium observed systematically through combinatorial analysis of high density genotype data. These analyses reveal the benefits of the new, randomly bred Collaborative Cross population.
New, highly diverse populations such as the Collaborative Cross and Diversity outcross alleviate these challenges with well-randomized breeding designs but carry with them the challenges of increased genetic diversity. These challenges enter into systems genetics experiments at many different levels. We are currently working on expression quantitation analyses that are unbiased with respect to genetic diversity and devising gene co-expression analyses using combinatorial and multivariate statistical approaches that take advantage of the deep quantitation enabled by new technologies.
Center related publications
Genetic analysis of complex traits in the emerging collaborative cross
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.
Genome Res. 2011 Aug;21(8):1223-38. PMCID: PMC3149489 [ Full Text ] [ Highlight in Nature Reviews Genetics ] [ datasets ]
Architecture of energy balance traits in emerging lines of the Collaborative Cross
Mathes WF, Aylor DL, Miller DR, Churchill GA, Chesler EJ, de Villena FP, Threadgill DW, Pomp D.
Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1124-34. PMCID: PMC3118585 [ Full Text ] [ datasets ]
Genetic analysis in the Collaborative Cross breeding population
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.
Genome Res. 2011 Aug;21(8):1223-38. PMCID: PMC3149490 [ Full Text ]
The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics
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.
Mamm Genome. 2008 Jun;19(6):382-9. PMCID: PMC2745091. [ Full Text ]