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Genome-wide co-expression analysis in multiple tissues.

ABSTRACT: Expression quantitative trait loci (eQTLs) represent genetic control points of gene expression, and can be categorized as cis- and trans-acting, reflecting local and distant regulation of gene expression respectively. Although there is evidence of co-regulation within clusters of trans-eQTLs, the extent of co-expression patterns and their relationship with the genotypes at eQTLs are not fully understood. We have mapped thousands of cis- and trans-eQTLs in four tissues (fat, kidney, adrenal and left ventricle) in a large panel of rat recombinant inbred (RI) strains. Here we investigate the genome-wide correlation structure in expression levels of eQTL transcripts and underlying genotypes to elucidate the nature of co-regulation within cis- and trans-eQTL datasets. Across the four tissues, we consistently found statistically significant correlations of cis-regulated gene expression to be rare (<0.9% of all pairs tested). Most (>80%) of the observed significant correlations of cis-regulated gene expression are explained by correlation of the underlying genotypes. In comparison, co-expression of trans-regulated gene expression is more common, with significant correlation ranging from 2.9%-14.9% of all pairs of trans-eQTL transcripts. We observed a total of 81 trans-eQTL clusters (hot-spots), defined as consisting of > or =10 eQTLs linked to a common region, with very high levels of correlation between trans-regulated transcripts (77.2-90.2%). Moreover, functional analysis of large trans-eQTL clusters (> or =30 eQTLs) revealed significant functional enrichment among genes comprising 80% of the large clusters. The results of this genome-wide co-expression study show the effects of the eQTL genotypes on the observed patterns of correlation, and suggest that functional relatedness between genes underlying trans-eQTLs is reflected in the degree of co-expression observed in trans-eQTL clusters. Our results demonstrate the power of an integrative, systematic approach to the analysis of a large gene expression dataset to uncover underlying structure, and inform future eQTL studies.

SUBMITTER: Grieve IC

PROVIDER: S-EPMC2603584 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Genome-wide co-expression analysis in multiple tissues.

Grieve Ian C IC Dickens Nicholas J NJ Pravenec Michal M Kren Vladimir V Hubner Norbert N Cook Stuart A SA Aitman Timothy J TJ Petretto Enrico E Mangion Jonathan J

PloS one 20081229 12

Expression quantitative trait loci (eQTLs) represent genetic control points of gene expression, and can be categorized as cis- and trans-acting, reflecting local and distant regulation of gene expression respectively. Although there is evidence of co-regulation within clusters of trans-eQTLs, the extent of co-expression patterns and their relationship with the genotypes at eQTLs are not fully understood. We have mapped thousands of cis- and trans-eQTLs in four tissues (fat, kidney, adrenal and l ...[more]

PMID: 19112506

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Project description:Bracoviruses are domesticated viruses found in parasitic wasp genomes. They are composed of genes of nudiviral origin that are involved in particle production and proviral segments containing virulence genes that are necessary for parasitism success. During particle production, proviral segments are amplified and individually packaged as DNA circles in nucleocapsids. These particles are injected by parasitic wasps into host larvae together with their eggs. Bracovirus circles of two wasp species were reported to undergo chromosomal integration in parasitized host hemocytes, through a conserved sequence named the host integration motif (HIM). Here, we used bulk Illumina sequencing to survey integrations of Cotesia typhae bracovirus circles in the DNA of its host, the maize corn borer (Sesamia nonagrioides), 7 days after parasitism. First, assembly and annotation of a high-quality genome for C. typhae enabled us to characterize 27 proviral segments clustered in proviral loci. Using these data, we characterized large numbers of chromosomal integrations (from 12 to 85 events per host haploid genome) for all 16 bracovirus circles containing a HIM. Integrations were found in four S. nonagrioides tissues and in the body of a caterpillar in which parasitism had failed. The 12 remaining circles do not integrate but are maintained at high levels in host tissues. Surprisingly, we found that HIM-mediated chromosomal integration in the wasp germ line has occurred accidentally at least six times during evolution. Overall, our study furthers our understanding of wasp-host genome interactions and supports HIM-mediated chromosomal integration as a possible mechanism of horizontal transfer from wasps to their hosts. IMPORTANCE Bracoviruses are endogenous domesticated viruses of parasitoid wasps that are injected together with wasp eggs into wasp host larvae during parasitism. Several studies have shown that some DNA circles packaged into bracovirus particles become integrated into host somatic genomes during parasitism, but the phenomenon has never been studied using nontargeted approaches. Here, we use bulk Illumina sequencing to systematically characterize and quantify bracovirus circle integrations that occur in four tissues of the Mediterranean corn borer (Sesamia nonagrioides) during parasitism by the Cotesia typhae wasp. Our analysis reveals that all circles containing a HIM integrate at substantial levels (from 12 to 85 integrations per host cell, in total) in all tissues, while other circles do not integrate. In addition to shedding new light on wasp-bracovirus-host interactions, our study supports HIM-mediated chromosomal integration of bracovirus as a possible source of wasp-to-host horizontal transfer, with long-term evolutionary consequences.

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Genome-wide co-expression analysis in multiple tissues.

Publications

Genome-wide co-expression analysis in multiple tissues.

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