Evaluation of expression quantitative trait loci within two interacting blood pressure quantitative trait loci
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE7628 | GEO | 2008/03/04
SECONDARY ACCESSION(S): PRJNA100255
REPOSITORIES: GEO
Similar Datasets
Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the âbiological signatureâ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Pairs of Cy5 and Cy3 labeled targets were co-hybridized onto either a custom long oligonucleotide microarray for the interrogation of 231 genes encompassed by QTL1 and QTL2, or a TIGR rat cDNA array consisting of 26,401 probe elements representing 20,465 unique non-QTL genes. A âflip-dyeâ or âbalanced blockâ design was used as the experimental method of choice to account for potential dye-bias labeling effects. Six âbalanced blockâ normalized files are submitted for the long oligonucleotide array interrogating the hearts from S versus S.LEW(5)x6x9 animals, fourteen âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x9 animals, and twelve âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x11 animals. GPR and MEV files cannot be located.
2010-06-25 | E-GEOD-7628 | biostudies-arrayexpress
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
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
Project description:Rats vary in their susceptibilities to Toxoplasma gondii infection depending on the rat strain. Compared to the T. gondii-susceptible Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii. Thus, these two rat strains are ideal models for elucidating host mechanisms that are important for host resistance to T. gondii infection. Therefore, in an attempt to unravel molecular factors directing the protective early innate immune responses in the LEW rat, we performed RNA sequencing analysis of the LEW versus BN rat, with or without T. gondii infection.
2017-07-24 | GSE100203 | GEO
Project description:Evidence from multiple linkage and genome-wide association studies suggest that human chromosome 2 (HSA2) contains alleles that influence blood pressure (BP). Homologous to a large segment of HSA2 is rat chromosome 9 (RNO9), to which a BP quantitative trait locus (QTL) was previously mapped. The objective of the current study was to further resolve this BP QTL. Eleven congenic strains with introgressed segments spanning <81.8kb to <1.33Mb were developed by introgressing genomic segments of RNO9 from the Dahl salt-resistant (R) rat onto the genome of the Dahl salt-sensitive (S) rat and tested for BP. The congenic strain with the shortest introgressed segment spanning <81.8kb significantly lowered BP of the hypertensive S rat by 25 mm Hg and significantly increased its mean survival by 45 days. In contrast, two other congenic strains had increased BP compared with the S. We focused on the <81.8kb congenic strain which represents the shortest genomic segment to which a BP QTL has been definitively mapped to date in any species. Sequencing of this entire region in both S and R rats detected 563 variants. The region did not contain any known or predicted rat protein coding genes. Further, a whole genome renal transcriptome analysis between S and the <81.8kb S.R congenic strain revealed alterations in several critical genes implicated in renal homeostasis. Taken together, our results provide the basis for future studies to examine the relationship between the candidate variants within the QTL region and the renal differentially expressed genes as potential causal mechanisms for BP regulation.
2010-07-15 | GSE22515 | GEO
Project description:The study of natural genetic variation for plant disease resistance responses is a complementary approach to utilizing mutants to elucidate genetic pathways. While some key genes involved in pathways controlling disease resistance, and signaling intermediates such as salicylic acid (SA) and jasmonic acid (JA), have been identified through mutational analyses, the use of genetic variation in natural populations permits the identification of change-of-function alleles, which likely act in a quantitative manner. Whole genome microarrays, such as Affymetrix GeneChips, allow for molecular characterization of the disease response at a genomics level and characterization of differences in gene expression due to natural variation. Differences in the level of gene expression, or expression level polymorphisms (ELPs), can be mapped in a segregating population to identify regulatory quantitative trait loci (expression QTLs, eQTLs) affecting host resistance responses. We surveyed recombinant inbred lines (RILs) from a population derived from a cross of inbred Arabidopsis accessions Bayreuth-0 (Bay-0) and Shahdara (Sha) in order to map eQTLs controlling ELPs. We treated vegetatively grown plants with either SA or a control solution (Silwet), and harvested the plants 28 hours after chemical treatment. We present Affymetrix GeneChip microarray expression data for 2 biological replications of the control (Silwet) samples for 63 RILs, plus replicated Bay-0 and Sha control samples grown at the same time as the RILs. These GeneChips representing 63 RILs, along with the GeneChips in Accession E-TABM-62 which represent an additional 148 RILs, form a 211 RIL dataset from which we mapped eQTLs.
2007-04-11 | E-TABM-126 | biostudies-arrayexpress
Project description:Analyses of QTLs for expression levels (eQTLs) of the genes reveal genetic relationship between expression variation and the regulator, thus unlocking the information for identifying the regulatory network. Oligo-nucleotide expression microarrays hybridized with RNA can simultaneously provide data for molecular markers and transcript abundance. In this study, we used Affymetrix GeneChip Rice Genome Array to analyze eQTLs in rice shoots at 72 h after germination from 110 recombinant inbred lines (RILs) derived from a cross between Zhenshan 97 and Minghui 63. Totally 1,632 single feature polymorphisms (SFPs) plus 23 PCR markers were identified and placed into 601 recombinant bins, spanning 1,459 cM in length, which were used as markers to genotype the RILs. We obtained 16,372 expression traits (e-traits) each with at least one eQTL, resulting in 26,051 eQTLs in total, including both cis- and trans-eQTLs. We also identified 171 eQTL hotspots among rice genome, each of which controls transcript variations of many e-traits. Gene Ontology analysis revealed enrichment of certain functional categories of genes in some of the eQTL hotspots. In particular, eQTLs for e-traits involving DNA metabolic process was significantly enriched in several eQTL hotspots on chromosomes 3, 5 and 10. Several transcription factors colocalizing with cis-eQTLs showed significant correlations with hundreds of e-traits, indicating possible co-regulation. We also detected correlations between the QTLs for shoot dry weight and eQTLs, revealing possible candidate genes for the trait. These results provided the clues for identification and characterization of regulatory network in the whole genome at the transcriptional level. To dissect the genetic variation between the two rice indica varieties Minghui 63 and Zhenshan 97, a total of 110 RILs from Minghui 63 and Zhenshan 97 and parents were sampled. And the Affymetrix Genechip rice Genome Array was used to investigate their dynamic transcript levels. Two independent biological replicates were sampled from each RIL, and three replicates for each parent.resulting in a dataset of 226 microarrays.
2011-06-24 | E-GEOD-22564 | biostudies-arrayexpress
Project description:The overlap of congenic regions in an earlier substitution mapping study suggested the location of two blood pressure quantitative trait loci (QTL)-containing regions in the q-terminus of rat chromosome 3, QTL1 and the more distal, QTL2. Male SS/jr rats and two congenic substrain rats S.R(D3Mco36-D3Mco46) and S.R(D3Mco36-D3Got166) were maintained on a low salt (0.4% NaCl Harlan Teklad diet TD7034) diet until 39-41 days of age and then fed an intermediate (2% NaCl Harlan Teklad diet TD94217) salt diet for 28 days. These 3 rat strains will be hereafter referred to as S, S.R(ET3x1), and S.R(ET3x2), respectively. Both congenic substrains carry SR/jr (R)-rat alleles for QTL2 on an S-rat genetic background, while S.R(ET3x2) also carries R-rat alleles for QTL1. Renal gene expression analysis was used to identify differentially expressed genes or genes with altered activity within the S.R(ET3x2) congenic region. Keywords: strain differences in response to dietary changes
2015-08-28 | GSE12423 | GEO
Project description:Evidence from multiple linkage and genome-wide association studies suggest that human chromosome 2 (HSA2) contains alleles that influence blood pressure (BP). Homologous to a large segment of HSA2 is rat chromosome 9 (RNO9), to which a BP quantitative trait locus (QTL) was previously mapped. The objective of the current study was to further resolve this BP QTL. Eleven congenic strains with introgressed segments spanning <81.8kb to <1.33Mb were developed by introgressing genomic segments of RNO9 from the Dahl salt-resistant (R) rat onto the genome of the Dahl salt-sensitive (S) rat and tested for BP. The congenic strain with the shortest introgressed segment spanning <81.8kb significantly lowered BP of the hypertensive S rat by 25 mm Hg and significantly increased its mean survival by 45 days. In contrast, two other congenic strains had increased BP compared with the S. We focused on the <81.8kb congenic strain which represents the shortest genomic segment to which a BP QTL has been definitively mapped to date in any species. Sequencing of this entire region in both S and R rats detected 563 variants. The region did not contain any known or predicted rat protein coding genes. Further, a whole genome renal transcriptome analysis between S and the <81.8kb S.R congenic strain revealed alterations in several critical genes implicated in renal homeostasis. Taken together, our results provide the basis for future studies to examine the relationship between the candidate variants within the QTL region and the renal differentially expressed genes as potential causal mechanisms for BP regulation. Six male S control and 6 male congenic S.R(9)x3x2Bx1x8 rats born on the same day were selected, weaned at 30 days of age, and caged with 1 congenic and 1 S rat per cage. They were raised on a High-salt (2%) diet (Harlan Teklad diet TD 7034; Harlan–Sprague-Dawley) and sacrificed at 53 days of age and total RNAs were isolated from the kidney. The isolated RNA from two animals were pooled together and considered as one biological sample. Three such RNA samples from S and congenic rats were used for the cRNA preparation. cRNA was prepared and fragmented as suggested by Affymetrix technical manual, and simultaneously hybridized (15 µg adjusted cRNA for each chip) to Rat Expression Array 230 2.0 (3' IVT Expression Analysis). Statistical analyses of the microarray data were performed using R statistical package (version 2.8.1).
2010-07-15 | E-GEOD-22515 | biostudies-arrayexpress
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 | GSE61742 | GEO