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:Absence of Sox3 in mice only results in subtle phenotype, presumably due to the rescue effects from the family members, SOXB1, which consist of Sox1, Sox2 and Sox3. Obvious defect in Sox3-KO mice is seen only in the testes where Sox1 and Sox2 are not co-expressed. The genetic dysregulation underlying this testis defects is unknown. We also hypothesize that this genetic dysregulation can be rescued by the other SOXB1 members. We performed microarray analysis to compare Sox3-KO mouse testes with the WT. We also generated Sox3-Sox2KI mice in which the Sox3 ORF is replaced with Sox2 ORF. Microarray was also performed to these knock-in testis samples to find out whether Sox2 can rescue genetic dysregulation resulting from the absence of Sox3.
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: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.
