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Pre-Collaborative Cross liver gene expression

ABSTRACT: The Collaborative Cross (CC) recombinant inbred panel was conceived as an ideal resource for mammalian system genetics. The pre-CC is a proof-of-concept experiment involving CC lines that have undergone at least five generations of inbreeding. Siblings from these lines were each involved in one of four distinct phenotyping arms, then genotyped on a high-density Affymetrix platform. The genetic profile of these emerging lines reveals high diversity, balanced allele frequencies, and well-distributed recombination – all ideal qualities for a mapping panel. We have mapped white spot, a discrete trait; body weight, a highly polygenic complex trait; and more than 11,000 liver gene expression traits. These analyses provide a glimpse of the potential mapping power and resolution of the CC. The goal of this project was to identify eQTLs for genome-wide gene expression from liver tissue in pre-CC mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE22297 | GEO | 2010/12/01

SECONDARY ACCESSION(S): PRJNA127417

REPOSITORIES: GEO

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Pre-Collaborative Cross liver gene expression

Project description:The Collaborative Cross (CC) recombinant inbred panel was conceived as an ideal resource for mammalian system genetics. The pre-CC is a proof-of-concept experiment involving CC lines that have undergone at least five generations of inbreeding. Siblings from these lines were each involved in one of four distinct phenotyping arms, then genotyped on a high-density Affymetrix platform. The genetic profile of these emerging lines reveals high diversity, balanced allele frequencies, and well-distributed recombination – all ideal qualities for a mapping panel. We have mapped white spot, a discrete trait; body weight, a highly polygenic complex trait; and more than 11,000 liver gene expression traits. These analyses provide a glimpse of the potential mapping power and resolution of the CC. The goal of this project was to identify eQTLs for genome-wide gene expression from liver tissue in pre-CC mice. Gene expression profiling from liver tissue from pre-CC males. Pre-Collaborative Cross (CC) mice are partially inbred strains created by intercrossing eight founder (parental) strains: 129S1/SvImJ, (129S1), A/J (AJ), C57BL/6J (B6), CAST/Ei (CAST), NOD/LtJ (NOD), NZO/H1LtJ (NZO), PWK/Ph (PWK), and WSB/Ei (WSB). Sister-brother mating in 220 families was done for 4-11 generations. One animal was sampled from 157 pre-CC strain. Hybridizations were performed at the Gene Expression Core Facility at The Jackson Laboratory. Samples were divided in six batches of about 11 to 24 samples. Two batches were performed per day. Probe-level data was summarized by a custom CDF file based on Ensembl genes (NCBI 37, Ensembl 49; htttp://brainarray.mbni.med.umich.edu). The parental strains are not part of this submission.

2010-12-01 | E-GEOD-22297 | biostudies-arrayexpress

Pre-Collaborative Cross lung gene expression after allergen challenge

2013-11-15 | GSE51768 | GEO

Pre-Collaborative Cross lung gene expression after allergen challenge

Project description:The Collaborative Cross (CC) recombinant inbred panel was conceived as an ideal resource for mammalian system genetics. The pre-CC is a proof-of-concept experiment involving CC lines that have undergone at least five generations of inbreeding. Siblings from these lines were each involved in one of four distinct phenotyping arms, then genotyped on a high-density Affymetrix platform. These mice were initially described in the following reference. Genome Research 2011 Aug;21(8):1213-22 (PMID: 21406540). The goal of this specific project was to identify gene expression QTL using lung tissue from pre-CC mice that were sensitized and challenged with house dust mite allergen (namely, Der p 1). We analyzed whole lung RNAs from 138 pre-Collaborative Cross mice using Illumina WG6v2 arrays. Pre-Collaborative Cross (CC) mice are partially inbred strains created by intercrossing eight founder (parental) strains: 129S1/SvImJ, (129S1), A/J (AJ), C57BL/6J (B6), CAST/Ei (CAST), NOD/LtJ (NOD), NZO/H1LtJ (NZO), PWK/Ph (PWK), and WSB/Ei (WSB). Sister-brother mating in 220 families was done for 5-12 generations. One animal was sampled from 138 unique pre-CC strains, each designated by the prefix OR which denotes Oak Ridge National Laboratory as the original source of these mice. The parental strains are not part of this submission. Hybridizations were performed at the National Human Genome Research InstituteM-bM-^@M-^Ys Gene Expression Core Facility.The resulting data were initially processed using Illumina Genome Studio software and then imported into R (v2.9.2) for post-processing. Normalization was conducted using RMA with quantile normalization and log2 transformation.

2013-11-15 | E-GEOD-51768 | biostudies-arrayexpress

Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains

Project description:A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences.

2016-10-17 | GSE77715 | GEO

RNA-seq on periodontal tisuues of susceptible and resistant collaborative cross mice after periodontal infection

Project description:We assessed alveolar bone changes of Collaborative cross (CC) lines in response to a mixed oral infection with a well-known periodontal pathogen. The CC lines showed significant variation in their response to the mixed infection. We then carried out RNA-seq analysis on periodontal tisuues of resistant CC lines, susceptible CC lines and two CC lines that showed bone formation after oral bacterial infection.

2020-02-19 | GSE145474 | GEO

Transcriptomics analysis of heart, kidney, and liver tissues from 58 Collaborative Cross strains

Project description:We report transcriptomic profiling from bulk heart, kidney, and liver tissues for 58 strains of the inbred mouse Collaborative Cross (CC). Each strain is represented by a male/female pair. Reads were first aligned to the pooled transcriptomes of the eight founder strains of the CC and then total gene counts were quantified using the EMASE and GBRS software tools. Total read counts can be further normalized for use in differential gene expression analysis, expression quantitative trait locus (eQTL) analysis, and integrative analyses with other -omic data sets measured on the same samples, including proteomics and phosphoproteomics.

2023-02-05 | GSE199702 | GEO

Genetic background shapes phenotypic response to diet for adiposity in the Collaborative Cross

Project description:Defined as chronic excessive accumulation of adiposity, obesity results from long-term imbalance between energy intake and expenditure. The mechanisms behind how caloric imbalance occurs are complex and influenced by numerous biological and environmental factors, especially genetics and diet. Population-based diet recommendations have had limited success partly due to the wide variation in physiological responses across individuals when they consume the same diet. Thus, it is necessary to broaden our understanding of how individual genetics and diet interact relative to the development of obesity for improving weight loss treatment. To determine how consumption of diets with different macronutrient composition alter adiposity and other obesity-related traits in a genetically diverse population, we analyzed body composition, metabolic rate, clinical blood chemistries, and circulating metabolites in 22 strains of mice from the Collaborative Cross (CC), a highly diverse recombinant inbred mouse population, before and after 8 weeks of feeding either a high protein or high fat high sucrose diet. At both baseline and post-diet, adiposity and other obesity-related traits exhibited a broad range of phenotypic variation based on CC strain; diet-induced changes in adiposity and other traits also depended largely on CC strain. In addition to estimating heritability at baseline, we also quantified the effect size of diet for each trait, which varied by trait and experimental diet. Our findings identified CC strains prone to developing obesity, demonstrate the genotypic and phenotypic diversity of the CC for studying complex traits, and highlight the importance of accounting for genetic differences when making dietary recommendations.

2020-11-05 | ST001607 | MetabolomicsWorkbench

Transcriptomic Profiling of Collaborative Cross Founder Mouse Embryonic Fibroblasts stimulated with IFN-g and IL28

Project description:Collaborative Cross (CC) mouse embryonic fibroblasts (MEF) cells obtained from the eight Founder animals [PWK/PhJ, NZO/HILtJ, NOD/ShiLtJ, WSB/EiJ, A/J, CAST, C57BL/6J, and 129/SvlmJ] were immortalized and the cell lines used to assess differences in transcriptional responses following treatment with mouse recombinant IFNg and IL28. We collected transcriptome profiles for 8 CC MEF cell lines stimulated with either IFNg or IL28 for a total of 16 different biological conditions. Treated and mock samples were collected at 18 hr post-treatment and RNAs extracted and subjected to microarray.

2016-05-26 | E-MTAB-4690 | biostudies-arrayexpress

Collaborative Cross Genomes Project

Project description:Whole-genome sequencing of mouse recombinant inbred lines from the Collaborative Cross panel.

| PRJEB14673 | ENA

Transcriptomic Profiling of Collaborative Cross Founder Mouse Embryonic Fibroblasts stimulated with Type I, II and III Interferons

Project description:Collaborative Cross (CC) mouse embryonic fiborolasts (MEF) cells obtained from the eight Founder animals [PWK/PhJ, NZO/HILtJ, NOD/ShiLtJ, WSB/EiJ, A/J, CAST, C57BL/6J, and 129/SvlmJ] were immortalized and the cell lines used to assess differences in transcriptional responses following treatment with type I, II and III recombinant mouse interferon. We collected transcriptome profiles for 8 CC MEF cell lines stimulated with either IFN-α or IFN-β for a total of 16 different biological conditions. Treated and mock samples were collected at 18 hr post-treatment and RNAs extracted and subjected to microarray.

2014-05-27 | E-GEOD-53057 | biostudies-arrayexpress

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