From genome to systems genetics The Collaborative Cross mouse genetic reference population


Meeting Abstract

S8.9  Tuesday, Jan. 6  From genome to systems genetics: The Collaborative Cross mouse genetic reference population CHESLER, E.J.*; ZHANG, Y.; PHILIP, V. M.; CULIAT, C.T.; LANGSTON, M.A.; CHURCHILL, G.A.; MANLY, K.F.; VOY, B.H; Oak Ridge National Lab., TN; Univ.of Tennessee, Knoxville; Univ. of Tennessee, Knoxville; Oak Ridge National Lab., TN; Univ. of Tennessee, Knoxville; The Jackson Lab., Bar Harbor, ME; Univ. of Buffalo, NY; Oak Ridge National Lab., TN cheslerej@ornl.gov

Systems genetics is a systems biological approach in which allelic variation is studied as a natural perturbation of a biological network. Aggregation of trait data, from biomolecular to whole-organism in a single population enables the simultaneous analysis of polygeneity and pleiotropy. Advances in genetic analysis made possible through the mouse genome have uncovered both the phenomenal potential of this approach to mouse genetics, along with enhanced knowledge of the limits to genetic analysis in extant populations. The Complex Trait Consortium has devised a novel mouse population to meet the demand for a resource suited to systems genetics, with high allelic diversity, power, precision, accuracy and independence of recombinations. Fundamental to many applications in systems genetics, the population must be retrievable, consisting of a panel of isogenic lines. The resulting population, the Collaborative Cross, consists of a systematic cross of 8 divergent inbred strains, followed by inbreeding to generate a highly polymorphic population with dense recombinations and haplotype breakpoints. Breeding of the population has been in progress at the Oak Ridge National Laboratory since 2005, with additional lines being produced at other sites. Phenotypic characterization has been performed through the course of breeding and includes behavioral, physiological and morphological traits. Genotypic characterization of the population has allowed a comparison of genetic architectures with existing mouse genetic reference populations and is expected to provide insight into the underlying genetic architecture of vertebrate phenotypes.

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