The Genome Architecture of the Collaborative Cross Mouse Genetic Reference Population

ABSTRACTThe Collaborative Cross (CC) is a mouse genetic reference population whose range of applications includes quantitative trait loci (QTL) mapping. The design of a CC QTL mapping study involves multiple decisions, including which and how many strains to use, and how many replicates per strain to phenotype, all viewed within the context of hypothesized QTL architecture. Until now, these decisions have been informed largely by early power analyses that were based on simulated, hypothetical CC genomes. Now that more than 50 CC strains are available and more than 70 CC genomes have been observed, it is possible to characterize power based on realized CC genomes. We report power analyses based on extensive simulations and examine several key considerations: 1) the number of strains and biological replicates, 2) the QTL effect size, 3) the presence of population structure, and 4) the distribution of functionally distinct alleles among the founder strains at the QTL. We also provide general power estimates to aide in the design of future experiments. All analyses were conducted with our R package, SPARCC (Simulated Power Analysis in the Realized Collaborative Cross), developed for performing either large scale power analyses or those tailored to particular CC experiments.

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Collaborative Cross Mouse Populations as a Resource for the Study of Epilepsy

10.1101/690917 ◽

2019 ◽

Author(s):

Bin Gu ◽

John R. Shorter ◽

Lucy H. Williams ◽

Timothy A. Bell ◽

Pablo Hock ◽

...

Keyword(s):

Animal Models ◽

Critical Role ◽

Reference Population ◽

Collaborative Cross ◽

Whole Genome Sequence ◽

Whole Genome ◽

Unexpected Death ◽

F2 Population ◽

Complex Features ◽

Genetic Reference Population

ABSTRACTEpilepsy is a neurological disorder with complex etiologies and genetic architecture. Animal models have a critical role in understanding the pathophysiology of epilepsy. Here we studied epilepsy utilizing a genetic reference population of Collaborative Cross (CC) mice with publicly available whole genome sequences. We measured multiple epilepsy traits in 35 CC strains, and we identified novel animal models that exhibit extreme outcomes in seizure susceptibility, seizure propagation, epileptogenesis, and sudden unexpected death in epilepsy. We performed QTL mapping in an F2 population and identified seven novel and one previously identified loci associated with seizure sensitivity. We combined whole genome sequence and hippocampal gene expression to pinpoint biologically plausible candidate genes and candidate variants associated with seizure sensitivity. These resources provide a powerful toolbox for studying complex features of seizures and for identifying genes associated with particular seizure outcomes, and hence will facilitate the development of new therapeutic targets for epilepsy.

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Designing a QTL Mapping Study for Implementation in the Realized Collaborative Cross Genetic Reference Population

Current Protocols in Mouse Biology ◽

10.1002/cpmo.66 ◽

2019 ◽

Vol 9 (4) ◽

Cited By ~ 1

Author(s):

Morris Soller ◽

Hanifa J. Abu‐Toamih Atamni ◽

Ilona Binenbaum ◽

Aristotelis Chatziioannou ◽

Fuad A. Iraqi

Keyword(s):

Qtl Mapping ◽

Reference Population ◽

Collaborative Cross ◽

Mapping Study ◽

Genetic Reference Population

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Diet modulates cecum bacterial diversity and physiological phenotypes across the BXD mouse genetic reference population

PLoS ONE ◽

10.1371/journal.pone.0224100 ◽

2019 ◽

Vol 14 (10) ◽

pp. e0224100

Author(s):

Maria Elisa Perez-Munoz ◽

Autumn M. McKnite ◽

Evan G. Williams ◽

Johan Auwerx ◽

Robert W. Williams ◽

...

Keyword(s):

Bacterial Diversity ◽

Reference Population ◽

Genetic Reference Population ◽

Mouse Genetic

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Genetic regulation of homeostatic immune architecture in the lungs of Collaborative Cross mice

10.1101/2021.04.09.439180 ◽

2021 ◽

Author(s):

Brea K Hampton ◽

Kara L. Jensen ◽

Alan C. Whitmore ◽

Colton L. Linnertz ◽

Paul Maurizio ◽

...

Keyword(s):

Immune Cell ◽

Genetic Regulation ◽

Reference Population ◽

Collaborative Cross ◽

System Stability ◽

Mouse Strains ◽

Cell Populations ◽

Immune Homeostasis ◽

Heritable Variation ◽

Organ Systems

Variation in immune homeostasis, immune system stability, in organ systems such as the lungs is likely to shape the host response to infection at these exposed tissues. We evaluated immune homeostasis in immune cell populations in the lungs of the Collaborative Cross (CC) mouse genetic reference population. We found vast heritable variation in leukocyte populations with the frequency of many of these cell types showing distinct patterns relative to classic inbred strains C57BL/6J and BALB/cJ. We identified 28 quantitative trait loci (QTL) associated with variation in baseline lung immune cell populations, including several loci that broadly regulate the abundance of immune populations from distinct developmental lineages, and found that many of these loci have predictive value for influenza disease outcomes, demonstrating that genetic determinants of homeostatic immunity in the lungs regulate susceptibility to virus-induced disease. All told, we highlight the need to assess diverse mouse strains in understanding immune homeostasis and resulting immune responses.

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