Project description:Two inbred mouse strains, C57BL/6J and CAST/EiJ, were crossed to generate both initial and reciprocal F1 crosses. For each genetically distinct class of mice (F0 C57BL/6J, F0 CAST/EiJ, F1i - C57BL/6J x CAST/EiJ, F1r - CAST/EiJ x C57BL/6J, where the male parent is listed first), samples were collected from a single lobe of the liver from 6 male mice between the ages of 4 and 6 months. The 24 samples were then processed to generate strand-specific RNA-seq libraries, which were sequenced on the Illumina GAII platform using 72bp paired-end reads.
Project description:An undefined number of mammalian genes are expressed preferentially from one parental allele, in a process termed genomic imprinting. To shed light on the general principles of this process in a single cell type, we profiled allelic gene expression, DNaseI hypersensitivity (DHS), and CTCF binding in genetically defined murine trophoblast stem cells (TSCs). The data deposited in this entry are from CTCF ChIP-Seq and DNase-Seq experiments performed in the BC.1 cell line. All other data has been previously deposited as part of GEO Series GSE39406. The F1 TSC line profiled was generated from a cross between a C57BL/6J (B6) female and CAST/EiJ (Cast) male mouse.
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.
Project description:Genetically distinct individuals are differentially affected by the DNA damaging effects of exposure to environmental toxicants, but the mechanisms contributing to these differences are poorly understood. It is known that genetic variation affects the establishment of the gene regulatory landscape, and we hypothesized that this may significantly contribute to the observed heterogeneity in individual responses to exogenous cellular insults. In this study, we investigated how genetic variation and chromatin organization may dictate susceptibility to DNA damage. We measured DNA damage, mRNA and miRNA expression, and chromatin accessibility genome-wide in lung tissue from two genetically-divergent inbred mouse strains, C57BL/6J and CAST/EiJ, at baseline and in response to exposure to a model DNA-damaging chemical, 1,3-butadiene (BD). Our results show that unexposed CAST/EiJ and unexposed C57BL/6J mice have very different chromatin organization and transcription profiles in the lung. Importantly, in unexposed CAST/EiJ, which is more resistant to BD-induced DNA damage, we see increased transcription and a more accessible chromatin landscape around genes involved in detoxification pathways. Upon BD exposure, chromatin is significantly remodeled in C57BL/6J around these genes to more closely resemble that found in CAST/EiJ. This suggests that strain-specific differences in baseline chromatin organization and transcription contribute to the relative resistance of CAST/EiJ to the DNA damaging effects of BD. Based on these results, we propose more generally that differences in the baseline molecular state of key tissues, driven by unique genetic backgrounds, significantly contributes to inter-individual variability in response to DNA-damaging environmental agents.
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven M-bM-^@M-^Xhotspots,M-bM-^@M-^Y seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a M-bM-^@M-^XfertileM-bM-^@M-^Y subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility. Gene expression was measured in whole testis in males aged 70(M-BM-15) days. Samples include 294 WSB/EiJ x PWD/PhJ F2s, 11 PWD/PhJ x WSB/EiJ F2s, 8 WSB/EiJ, 8 PWD/PhJ, 6 PWD/PhJ x WSB/EiJ F1s and 4 WSB/EiJ x PWD/PhJ F1s.
Project description:We report testis H3K4me3 enrichment in an F1 male from a C57BL/6J (B6) x CAST/Eij (CAST) cross (B6 mother, CAST father). This mouse is heterozygous at PRDM9 for a humanized allele (Davies et al. Nature 2016) and the CAST allele. After filtering of promoter H3K4me3 regions, these data serve as a measure of PRDM9 binding enrichment on each homologue. We found that both crossovers and non-crossovers (observed by sequencing F2/F4/F5 genomic DNA) are depleted at "asymmetric" Double-Strand Break hotspots where PRDM9 primarily binds only one of the two homologues. This proves that PRDM9 plays an important role in promoting inter-homologue interactions and can explain why increasing PRDM9 binding asymmetry predicts hybrid infertility. See Li, Bitoun, Altemose et al. 2018 (pending) for a complete summary.
Project description:RNA-Seq was performed on mESCs generated from F1 hybrids from reciprocal crosses of C57BL/6J and CAST/EiJ, denoted B and C hereafter; cell lines are designated as BC or CB, with the maternal line symbolized first
Project description:We have identified candidate genes from the Feml2 QTL influencing femur length through allele specific expression analysis of growth plates in C57BL/6J x CAST/EiJ F1 hybrids. This work provides the foundation to identify novel genes affecting bone geometry.
Project description:We profiled genome-wide gene expression of 170 individual mid-gestation (embryonic day 11.5) whole mouse embryos derived from a 2-generation interspecies mouse cross and asked to what extent genetic variation drives four important parameters of regulatory architecture: allele-specific expression (ASE), imprinting, trans-regulatory effects, and maternal effect. The inbred strain C57BL/6J and wild-derived inbred strain CAST/EiJ were used in reciprocal crosses to generate F1 embryos. F1 progeny were backcrossed to C57BL/6J in reciprocal crosses to generate 154 N2 embryos. We employed a backcross design, in which N2 offspring have genotypically distinct parents, to enable comparison of gene expression for offspring from each side of the reciprocal cross. Our findings demonstrate that genetic variation contributes to widespread gene expression differences during mammalian embryogenesis. Transcriptome analysis of E11.5 mouse embryos: 16 F1 embryos from reciprocally crossed C57BL/6J and CastEi/J parents; and 154 N2 embryos from reciprocal backcross of F1s to the C57BL/6J parent.
Project description:To determine if genetic background can modulate severity of an infection, we studied the host responses to influenza infections in the eight genetically highly diverse Collaborative Cross (CC) founder mice. The CC founder (C57BL/6J, 129S1/SvlmJ, CAST/EiJ, PWK/PhJ) were intranasally infected with influenza A/HK/01/68 (H3N2) with 20μl virus solution (1x101 ffu) or mock infected (with PBS). After infection lung was collected at different time points (mock_d3), d3, d5).