Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of mouse strains for eQTL CNV Analysis

ABSTRACT: Background; Haplotype association mapping is a recently developed method that can be used to identify expression Quantitative Trait Loci (eQTLs). The underlying genomic structure of the haplotype can be defined by single nucleotide polymorphisms (SNPs), variable number tandem repeats (VNTRs) and copy number variations (CNVs). Microarray genotyping platforms are able to interrogate all three genomic polymorphisms simultaneously. Combined with gene expression data, these data allow for the elucidation of sites responsible for the regulation of transcription. Results; Thirty three inbred strains were genotyped on a microarray platform to assess possible contributions of polymorphic regions to gene expression. Over one hundred million statistical correlations were made between probe performance on genotyping and gene expression microarrays. This analysis provided 10,655 trans associations and 31 cis associations. Further investigation of one of the cis associations revealed that a 84kb region of MMU3 acts as a haplotype-specific locus control region for the glutathione-S-transferase mu family in multiple tissues. In the strains that share the minor haplotype, reductions in mRNA levels in members of the Gst mu family are observed. Conclusions; We have identified a haplotype containing a putative locus control region for the Gst mu family gene cassette. In the strains with affected haplotype, Gst mu expression is drastically reduced. The reduction in Gst mu levels has important relevance for pharmacology and toxicology studies. The reduction of Gst mu levels in general, and Gstm5 in particular, has implication in models of dopamine metabolism, Parkinsonâs disease, and chemical neurotoxicity. Experiment Overall Design: Samples GSM262266-GSM262267, GSM262270-GSM262272 representing liver gene expression Samples from 10 week old male mouse livers were analyzed in a confirmation study of an identified eQTL. Samples came from pools of three animals, and were compared across strains. Experiment Overall Design: The genotyping summary output file and associated .CEL files are linked below as supplementary files. Briefly: Experiment Overall Design: After hybridization and staining the arrays are scanned on an Affymetrix Scanner 3000 7G 4C using four distinct filters, one for each DNA base (A, C, G, T). These scanned images are saved at .dat files. A grid is superimposed on the .dat array image such that each element of the grid brackets a feature. Once the grid has been applied, GCOS computes one intensity value for each cell, and saves these values in a .CEL file. A .CEL file is generated for each possible base (A, C, G, T). Only the .CEL files are read by GTGS. Experiment Overall Design: The .CEL files computed by GCOS are then imported into GTGS and analyzed. The experiments are then clustered together and used to generate a normalized profile of each probe. From the clustered profiles a genotype call is made for every specific probe on an individual chip. These genotyped calls are then exported from GTGS into a .txt file containing assay id, sample id and relative intensity values for each DNA base over the entire set of SNPs analyzed.

ORGANISM(S): Mus musculus

SUBMITTER: Mathew Pletcher

PROVIDER: E-GEOD-10377 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Human pluripotent stem cells commonly undergo adaptive changes during prolonged passaging in vitro. We have developed a new laminin-521 based method for self-renewal of human pluripotent stem cells. SNP6.0 array was used to assess genetic stability of several human ES cell lines cultured in the new system with two lines (H1 and HS401) cultured on feeders (standard conditions) Two main objectives in this study: To compare the number of the CNVs in human ES cells at early and late passages; for example, samples HS980 p6 and HS980 p31 represent HS980 cells at passages 6 and 31, respectively. The overall conclusion is that the observed number of CNVs is similar in the cells at early and late passages. This analysis can be remade without the reference samples. To compare the number of CNVs in control human ES cells (H1 and HS401) grown under standard protocol with that in cells (HS980, HS983a, HS999, HS916, and HS1001) grown under a new, developed by us, protocol. Because the cells were from different individuals, we could not compare them directly. Instead, we compared them to a set of samples from 75 healthy individuals, and then with each other. For the Reference These samples had been hybridized in the same lab as our samples, but for a different project; and the data were kindly provided by Prof. Kere. However, the same overall conclusion would result from an other sufficiently large dataset of healthy human individuals. Please note that 75 healthy individual samples had been hybridized in the same lab as our samples and the data were kindly provided by Prof. Kere, which is linked as a Series supplementary file ('75_samples_ref.REF'). It is a Reference Model File that Affymetrix Genotyping Console software has created based on data from 75 healthy individuals (i.e. processed file based on the CEL files of the 75 healthy individuals). The file derives from the "CN/LOH Reference Model File Creation and Analysis (Batch Sample Mode)" process according to the Genotyping Console manual. It contains SNP-wise information on the observed distribution of hybridization intensities of a set of samples that are assumed to be diploid in copy number (for most part of their genomes at least). This file is then used to compare the intensities observed in the CEL files of interest to infer deviations from the reference as CNVs. Thus, in combination with the CEL files (from each ES cell line), this file enables the exact replication of the CNV analyses done for the various human ES cell lines study.

Project description:Genome-wide association study (GWAS) was performed in 120 patient-parents trio samples from Japanese schizophrenia pedigrees ABSTRACT: Schizophrenia is a devastating neuropsychiatric disorder with genetically complex traits. Genetic variants should explain a considerable portion of the risk for schizophrenia, and genome-wide association study (GWAS) is a potentially powerful tool for identifying the risk variants that underlie the disease. Here, we report the results of a three-stage analysis of three independent cohorts consisting of a total of 2,535 samples from Japanese and Chinese populations for searching schizophrenia susceptibility genes using a GWAS approach. Firstly, we examined 115,770 single nucleotide polymorphisms (SNPs) in 120 patient-parents trio samples from Japanese schizophrenia pedigrees. In stage II, we evaluated 1,632 SNPs (1,159 SNPs of p < 0.01 and 473 SNPs of p < 0.05 that located in previously reported linkage regions). The second sample consisted of 1,012 case-control samples of Japanese origin. The most significant p value was obtained for the SNP in the ELAVL2 [(embryonic lethal, abnormal vision, Drosophila)-like 2] gene located on 9p21.3 (p = 0.00087). In stage III, we scrutinized the ELAVL2 gene by genotyping gene-centric tagSNPs in the third sample set of 293 family samples (1,163 individuals) of Chinese descent and the SNP in the gene showed a nominal association with schizophrenia in Chinese population (p = 0.026). The current data in Asian population would be helpful for deciphering ethnic diversity of schizophrenia etiology. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from peripheral blood samples. SUPPLEMENTARY FILES: CEL files were processed by manufacture's protocol. Genotype data were analyzed with the GeneSpring GT (Varia) 2.0 software package developed by Agilent Technologies (Santa Clara, CA). Matrix tables for the Genetic programs were produced (Linkage format: http://bioinformatics.med.utah.edu/~alun/software/docs/linkage.html) File 1: Matrix file_SNP_Map.txt File 2: Matrix file_Family_Information.txt File 3: Matrix file_Pedigree_Format.txt (Genotyping data of Linkage format) Transmission disequilibrium test was performed using the R program (http://www.r-project.org). File 4: Matrix file_results.txt

Dataset Information

Transcription profiling of mouse strains for eQTL CNV Analysis

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure