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.
Project description:Analysis of changes in gene expression in skin epidermis upon conditional knockout of the essential Polycomb repressive complex 2 (PRC2) subunit Eed. Loss of Eed in skin epithelium leads to de-repression of key Merkel-differentiation genes, which are known PRC2 targets, and results in ectopic formation of Merkel cells that are associated with all hair types. Gene expression analysis: To determine the changes in gene expression in skin epidermis upon conditional knockout of Eed, total RNA was isolated from skin epidermis in four biologic replicates from cells in different conditions and hybridized to SurePrint G3 Mouse GE 8X60K microarrays (Agilent).
