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Transcription profiling of mouse mouse bone marrow macrophages from a strain intercross

ABSTRACT: Bone marrow macrophages were cultured from 16 week old apoE-deficient F2 mice from an AKRxDBA/2 intercross; Gene expression profiling was performed using Affy 430v2 arrays, and 1967 informative SNP markers were genotyped for each mouse; Supplementary file of SNP data attached below from ParAllele 5K mouse linkage panel Experiment Overall Design: Expression QTLs and sex effects on gene expression and eQTLs were determined

ORGANISM(S): Mus musculus

SUBMITTER: Jonathan David Smith

PROVIDER: E-GEOD-8512 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Expression data from mouse bone marrow macrophages from a strain intercross

Project description:Bone marrow macrophages were cultured from 16 week old apoE-deficient F2 mice from an AKRxDBA/2 intercross Gene expression profiling was performed using Affy 430v2 arrays, and 1967 informative SNP markers were genotyped for each mouse Supplementary file of SNP data attached below from ParAllele 5K mouse linkage panel Keywords: Genetic-genomic

2007-07-19 | GSE8512 | GEO

Impact of Regulatory Variation from RNA to Protein

Project description:Genetic variants that impact gene regulation are important contributors to human phenotypic variation. For this reason, considerable efforts have been made to identify genetic associations with differences in mRNA levels of nearby genes, namely, cis expression quantitative trait loci (eQTLs). The phenotypic consequences of eQTLs are presumably due, in most cases, to their ultimate effects on protein expression levels. Yet, only few studies have quantified the impact of genetic variation on proteins levels directly. It remains unclear how faithfully eQTLs are reflected at the protein level, and whether there is a significant layer of cis regulatory variation acting primarily on translation or steady state protein levels. To address these questions, we measured ribosome occupancy by high-throughput sequencing, and relative protein levels by high-resolution quantitative mass spectrometry, in a panel of lymphoblastoid cell lines (LCLs) in which we had previously measured transcript expression using RNA sequencing. We then mapped genetic variants that are associated with changes in transcript expression (eQTLs), ribosome occupancy (rQTLs), or protein abundance (pQTLs). Most of the QTLs we detected are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, we found that eQTLs tend to have significantly reduced effect sizes on protein levels, suggesting that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we confirmed the presence of a class of cis QTLs that specifically affect protein abundance with little or no effect on mRNA levels; most of these QTLs have little effect on ribosome occupancy, and hence may arise from differences in post-translational regulation.

2014-12-19 | PXD001406 | Pride

Transcription profiling of mouse hippocampus, lung and liver for expression quanitative trait analysis

Project description:A proportion of the genetic variants underlying complex phenotypes do so through their effects on gene expression, so an important challenge in complex trait analysis is to discover the genetic basis for the variation in transcript abundance. So far, the potential of mapping both quantitative trait loci (QTLs) and expression quantitative trait loci (eQTLs) in rodents has been limited by the low mapping resolution inherent in crosses between inbred strains. We provide a megabase resolution map of thousands of eQTLs in hippocampus, lung, and liver samples from heterogeneous stock (HS) mice in which 843 QTLs have also been mapped at megabase resolution. We exploit dense mouse SNP data to show that artifacts due to allele-specific hybridization occur in _30% of the cis-acting eQTLs and, by comparison with exon expression data, we show that alternative splicing of the 3_ end of the genes accounts for <1% of cis-acting eQTLs. Approximately one third of cis-acting eQTLs and one half of trans-acting eQTLs are tissue specific. We have created an important systems biology resource for the genetic analysis of complex traits in a key model organism.

2009-10-22 | E-MTAB-88 | biostudies-arrayexpress

Genetic Loci that Regulate Ectopic Calcification in Response to Knee Trauma in LG/J by SM/J Advanced Intercross Mice

Project description:Ectopic calcification in synovial tissues is devastating to diarthrodial joints. While some forms of synovial ectopic calcification have genetically simple basis, most cases manifest as complex traits with environmental and multigenic components. The location of causal loci or the physiological processes affected by allelic variants is poorly understood. Here, we report on genetic susceptibility to ectopic calcification in the LG/J and SM/J advanced intercross mice. Using 347 mice in 98 full-sibships, destabilization of medial meniscus was performed to induce joint injury. We performed quantitative trait locus (QTL) analysis to map calcification phenotypes to discrete genomic locations. To validate the functional significance of the selected QTL candidate genes, we compared mRNA expression between parental LG/J and SM/J inbred strains. Our findings showed that joint destabilization instigated ectopic calcifications as detected and quantified by micro-CT. Overall, we detected 20 QTLs affecting synovial and meniscus calcification phenotypes with 11 QTLs linked to synovial calcification. Functional and bioinformatic analyses of single nucleotide polymorphism identified functional classifications relevant to angiogenesis (Myo1e, Kif26b, Nprl3, Stab2, Fam105b), bone metabolism/calcification (Tle3, Tgfb2, Lipc, Nfe2l1, Ank, Fam105b), arthritis (Stab2, Tbx21, Map4k4, Hoxb9, Larp6, Col1a2, Adam10, Timp3, Nfe2l1, Trpm3), and ankylosing-spondylitis (Ank, Pon1, Il1r2, Tbkbp1) indicating that ectopic calcification involves multiple mechanisms. Furthermore, the expression of 11 candidate genes was significantly different between LG/J and SM/J. Correlation analysis showed that Aff3, Fam81a, Syn3, and Ank were correlated with synovial calcification. Our findings of multiple genetic loci affecting the phenotype suggest the involvement of multiple genes contributing to its pathogenesis.

2015-01-09 | GSE64793 | GEO

Expression profiling of brain tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

Project description:The (C57BL/6J X C3H/HeJ)F2 intercross consists of 334 animals of both sexes. All are ApoE null and received a high fat Western diet from 8-24 weeks of age.

2006-07-07 | GSE3087 | GEO

Expression profiling of Adipose tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

Project description:The (C57BL/6J X C3H/HeJ)F2 intercross consists of 334 animals of both sexes. All are ApoE null and received a high fat Western diet from 8-24 weeks of age.

2006-07-07 | GSE3086 | GEO

Expression profiling of liver tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

Project description:The (C57BL/6J X C3H/HeJ)F2 intercross consists of 334 animals of both sexes. All are ApoE null and received a high fat Western diet from 8-24 weeks of age.

2006-07-27 | GSE2814 | GEO

Expression profiling of Muscle tissue from (C57BL/6J X C3H/HeJ)F2 mice on ApoE null backgrounds

Project description:The (C57BL/6J X C3H/HeJ)F2 intercross consists of 334 animals of both sexes. All are ApoE null and received a high fat Western diet from 8-24 weeks of age.

2006-07-07 | GSE3088 | GEO

Structural genomic variation analysis in patients with bone marrow failure using Illumina Infinium SNP Arrays [Illumina Quad610 Beadchip]

Project description:To better understand the natural history of bone marrow failure syndromes, we analyzed 124 single nucleotide polymorphism arrays (SNP-A) from a comprehensively characterized cohort of 91 patients who had SNP-A for clinical evaluation of BMFS. 67 samples from 51 patients were genotyped with the Quad610, and 57 samples from 54 patients were genotyped with the Omni1-Quad. This submission includes 67 samples from 51 patients that were genotyped with Illumina Quad610 Beadchip.

2014-01-01 | GSE48483 | GEO

Structural genomic variation analysis in patients with bone marrow failure using Illumina Infinium SNP Arrays [Omni1-Quad]

Project description:To better understand the natural history of bone marrow failure syndromes, we analyzed 124 single nucleotide polymorphism arrays (SNP-A) from a comprehensively characterized cohort of 91 patients who had SNP-A for clinical evaluation of BMFS. 67 samples from 51 patients were genotyped with the Quad610, and 57 samples from 54 patients were genotyped with the Omni1-Quad. This submission includes 55 samples from 54 patients that were genotyped with Omni1-Quad.

2014-01-01 | GSE48482 | GEO

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