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 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:Sequencing files provided here are mouse liver RNA-seq in two mouse strains: C57BL/6J and CAST/EiJ. This is part of a larger study published in PLoS Genetics (2021) "Harnessing natural variation to identify cis regulators of sex-biased gene expression in a multi-strain mouse liver model" that includes DNase-seq and H3K27ac ChIP-seq in mouse liver from the same two strains. This allows us to identify strain-shared ("core") and strain-unique sex-biased genes and enhancers.
Project description:Technical control for allelic detection using Smart-seq3. Liver RNA from pure C57BL6/J and CAST/EiJ strains was combined at varying ratios (0:1, 1:7, 1:3, 3:5, 1:1, 5:3, 3:1, 7:1, 1:0) for a total of 200 pg RNA per sample.
Project description:Sequencing files provided here are mouse liver ChIP-seq for the activating histone mark H3K27ac in two mouse strains: C57BL/6J and CAST/EiJ. This is part of a larger study published in PLoS Genetics (2021) "Harnessing natural variation to identify cis regulators of sex-biased gene expression in a multi-strain mouse liver model" that includes RNA-seq and DNase-seq in mouse liver from the same two strains. This allows us to identify strain-shared ("core") and strain-unique sex-biased genes and enhancers.
Project description:Sequencing files provided here are mouse liver DNase-seq in two mouse strains: C57BL/6J and CAST/EiJ. This is part of a larger study published in PLoS Genetics (2021) "Harnessing natural variation to identify cis regulators of sex-biased gene expression in a multi-strain mouse liver model" that includes RNA-seq and H3K27ac ChIP-seq in mouse liver from the same two strains. This allows us to identify strain-shared ("core") and strain-unique sex-biased genes and enhancers.
Project description:Male C3H/HeOuJ and CAST/EiJ mice were treated with diethylnitrosamine to induce liver tumours. We collected liver samples from untreated P15 mice for control experiments. Liver tissue samples were snap frozen in liquid nitrogen and total RNA was extracted using the AllPrep 96 DNA/RNA Kit (Qiagen) according to the manufacturer’s instructions. Libraries were prepared using the TruSeq Stranded Total RNA Library Prep Kit with Ribo-Zero Gold (Illumina) and sequenced on an Illumna HiSeq4000 to produce 150bp paired-end reads.
Project description:Susceptibility to tumor development varies among mice strains. Using inbred NIH and wild-derived outbred Mus spretus backcrosses, skin cancer-susceptibility loci were mapped [Nagase et al. 1995. Nat Genet 10: 424-429; Nagase et al. 1999. Proc Natl Acad Sci USA 96: 15032-15037], and Skts13 was identified as the Aurka gene using a conventional linkage in conjunction with haplotype analysis [Ewart-Toland et al. 2003. Nat Genet 34: 403-412]. In the present study, we examined another wild-derived outbred Mus musculus castaneus in which 10.3% of the analyzed SNPs showed heterogeneity among the colony. All mice examined were completely resistant to the two-stage skin carcinogenesis protocol using 7.12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA), and this resistant phenotype was dominant when we crossed them with the highly susceptible strain FVB. By scanning F1 backcross progeny between M. m. castaneus and FVB, we found a highly significant linkage for tumor multiplicity on Chromosome 4, which was overlapped with the Skts-fp1 locus, found in the previous study using FVB and PWK cross [Fujiwara et al. 2007. BMC Genet 8: 39]. The linkage was observed in all pedigrees from the five F1 founders, while the linkage for papilloma size on Chromosome 4 was mapped only in pedigrees from founders 1 and 2. By scanning the whole Chromosome 4 of the five F1 founders, founders 1- and 2-specific haplotype block was found between D4Mit293 (20.6 Mbp) and D4Mit171 (22.4 Mbp). In this study we exploited the outbred nature of M. m. castaneus stock to identify a haplotype contributing to papilloma size on mouse Chromosome 4. These data illustrate the strength of using outbred mice in identification of the genetic component of a mouse complex trait such as the skin cancer-susceptibility phenotype.
