SYSGENET: a meeting report from a new European network for systems genetics

Schughart, Klaus

doi:10.1007/s00335-010-9273-7

Cited by 10 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Host defense is strongly influenced by genetic differences and several studies have shown that the genetic background and sequence difference among humans and other host species modulate susceptibility and resistance to infectious diseases, allergens, and xenobiotics. Systems genetics is a modern extension of complex trait analysis that jointly analyzes and integrates large sets of genotypes and phenotypes to explain and predict variation in outcome measures and disease severity (for review see [ 1 , 2 ]). A typical systems genetics study relies on extensive single nucleotide polymorphism (SNP) data sets, matched data on RNA expression in key cells, tissues, or organs and a core set of key dependent measures such as disease susceptibility [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis of the mouse lung transcriptome reveals novel molecular gene interaction networks and cell-specific expression signatures

et al. 2011

Self Cite

View full text Add to dashboard Cite

BackgroundThe lung is critical in surveillance and initial defense against pathogens. In humans, as in mice, individual genetic differences strongly modulate pulmonary responses to infectious agents, severity of lung disease, and potential allergic reactions. In a first step towards understanding genetic predisposition and pulmonary molecular networks that underlie individual differences in disease vulnerability, we performed a global analysis of normative lung gene expression levels in inbred mouse strains and a large family of BXD strains that are widely used for systems genetics. Our goal is to provide a key community resource on the genetics of the normative lung transcriptome that can serve as a foundation for experimental analysis and allow predicting genetic predisposition and response to pathogens, allergens, and xenobiotics.MethodsSteady-state polyA+ mRNA levels were assayed across a diverse and fully genotyped panel of 57 isogenic strains using the Affymetrix M430 2.0 array. Correlations of expression levels between genes were determined. Global expression QTL (eQTL) analysis and network covariance analysis was performed using tools and resources in GeneNetwork http://www.genenetwork.org.ResultsExpression values were highly variable across strains and in many cases exhibited a high heri-tability factor. Several genes which showed a restricted expression to lung tissue were identified. Using correlations between gene expression values across all strains, we defined and extended memberships of several important molecular networks in the lung. Furthermore, we were able to extract signatures of immune cell subpopulations and characterize co-variation and shared genetic modulation. Known QTL regions for respiratory infection susceptibility were investigated and several cis-eQTL genes were identified. Numerous cis- and trans-regulated transcripts and chromosomal intervals with strong regulatory activity were mapped. The Cyp1a1 P450 transcript had a strong trans-acting eQTL (LOD 11.8) on Chr 12 at 36 ± 1 Mb. This interval contains the transcription factor Ahr that has a critical mis-sense allele in the DBA/2J haplotype and evidently modulates transcriptional activation by AhR.ConclusionsLarge-scale gene expression analyses in genetic reference populations revealed lung-specific and immune-cell gene expression profiles and suggested specific gene regulatory interactions.

show abstract

Section: Introductionmentioning

confidence: 99%

Genome-wide analysis of the mouse lung transcriptome reveals novel molecular gene interaction networks and cell-specific expression signatures

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…family (Peirce et al, 2004), the Hybrid Mouse Diversity Panel (Bennett et al, 2015;Ghazalpour et al, 2012), and the Collaborative Cross (Churchill et al, 2004;Schughart and Williams, 2017;Valdar et al, 2006). The main limitation has been relatively modest mapping power and precision-a simple problem caused by small numbers of strains.…”

Section: Numbers Of Strains and Replicates In Bxdmentioning

confidence: 99%

A platform for experimental precision medicine: The extended BXD mouse family

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Pearson’ correlation graphs were built constructed using the database obtained from the hypothalamus (INIA Hypothalamus Affy MoGene 1.0 ST (Nov10) database), striatum, liver, retina, spleen, neocortex, and pituitary of BXD inbred family, as previously published (Andreux et al, ). Datasets from a BXD published phenotypes (Schughart & Consortium, ) were also analyzed. The human dataset from hypothalamic tissue (GTEx Human Hypothalamus (Mar14) RPKM Log2 database) and 26 other tissues were evaluated, as previously published (GTEx Consortium, ) by Pearson’s correlations.…”

Section: Methodsmentioning

confidence: 99%

“…Datasets from a BXD published phenotypes (Schughart & Consortium, 2010) were also analyzed. The human dataset from hypothalamic tissue (GTEx Human Hypothalamus (Mar14) RPKM Log2 database) and 26 other tissues were evaluated, as previously published (GTEx Consortium, 2013) by Pearson's correlations.…”

Section: Bioinformatics Analysismentioning

confidence: 99%

Exercise activates the hypothalamic S1PR1–STAT3 axis through the central action of interleukin 6 in mice

Silva

Micheletti

Katashima

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Hypothalamic sphingosine-1-phosphate receptor 1 (S1PR1), the G protein-coupled receptor 1 of sphingosine-1-phosphate, has been described as a modulator in the control of energy homeostasis in rodents. However, this mechanism is still unclear. Here, we evaluate the role of interleukin 6 (IL-6) associated with acute physical exercise in the control of the hypothalamic S1PR1-signal transducer and activator of transcription 3 (STAT3) axis. Acute exercise session and an intracerebroventricular IL-6 injection increased S1PR1 protein content and STAT3 phosphorylation in the hypothalamus of lean and obese mice accompanied by a reduction in food consumption. Transcriptome analysis indicated a strong positive correlation between Il-6 and S1pr1 messenger RNA in several tissues of genetically diverse BXD mice strains and humans, including in the hypothalamus. Interestingly, exercise failed to stimulate the S1PR1-STAT3 axis in IL-6 knockout mice and the disruption of hypothalamic-specific IL-6 action blocked the anorexigenic effects of exercise. Taken together, our results indicate that physical exercise modulates the S1PR1 protein content in the hypothalamus, through the central action of IL-6.

show abstract

SYSGENET: a meeting report from a new European network for systems genetics

Cited by 10 publications

References 50 publications

Genome-wide analysis of the mouse lung transcriptome reveals novel molecular gene interaction networks and cell-specific expression signatures

Genome-wide analysis of the mouse lung transcriptome reveals novel molecular gene interaction networks and cell-specific expression signatures

A platform for experimental precision medicine: The extended BXD mouse family

Exercise activates the hypothalamic S1PR1–STAT3 axis through the central action of interleukin 6 in mice

Contact Info

Product

Resources

About