Project description:Caesium-137 (Cs-137) is one of the major radionuclides appearing in the natural environment after nuclear power plant accidents. However, the biological effects of low-dose internal irradiation with this radionuclide remain unclear. We developed an experimental model for studying low-dose internal irradiation using cultured human cells. The cells were incubated in the culture medium supplemented with unsealed Cs-137 chloride. We used the Monte Carlo simulation method for measuring internal irradiation because making direct measurements was not possible. The simulation revealed that 96.40%?99.70% of the internal irradiation involved ?-particles and other electrons. During the experiment, a gradual incorporation of Cs-137 in the cells, and the absorbed dose rate increased in a time-dependent manner. In addition, the number of ?-H2AX and 53BP1 nuclear foci in the cells increased by internal irradiation in a dose-dependent manner. Microarray analysis revealed time-dependent alterations in gene expression caused by the radiation. These results demonstrate that our experimental system can be useful in the investigation of the effects of low-dose internal irradiation.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
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 ‘hotspots,’ 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 ‘fertile’ 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.