Project description:The degree to which the level of genetic variation for gene expression is shared across multiple tissues has important implications for research investigating the role of expression on the aetiology of complex human traits and diseases. In the last few years, a number of studies have been published reporting the extent of overlap in expression quantitative trait loci (eQTL) identified in multiple tissues or cell types. Whilst these studies provide important information on the regulatory control of genes across tissues, their limited power means they can typically only explain a small proportion of genetic variation for gene expression. Here, using expression data from monozygotic twins (MZ), we investigate the genetic control of gene expression in lymphoblastoid cell lines (LCL) and whole blood (WB). We estimate the genetic correlation which represents the combined effects of all causal loci across the whole genome and is a measure of the level of common genetic control of gene expression between the two RNA sources. Our results show that, when averaged across the genome, mean levels of genetic correlation for gene expression in LCL and WB samples are close to zero. We support our results with evidence from gene expression in an independent sample of LCL, T-cells and Fibroblasts. In addition, we provide evidence that housekeeping genes, which maintain basic cellular functions, are more likely to have high genetic correlations between the RNA sources than non-housekeeping gene, implying a relationship between the transcript function and the degree to which a gene has tissue specific genetic regulatory control. In this study, the global genetic control of expression levels for 9555 genes were examined from two samples of RNA sources, collected on pairs of monozygotic (MZ) twins. From each individual, gene expression profiles were generated whole blood (WB), collected using the PAXgeneTM tube system, and lymphoblastoid cell lines (LCL). Using expression data collected from MZ twins is a powerful means of estimating the genetic contribution of expression variation. In particular, the observed phenotypic covariance in gene expression in LCLs and WBs between MZ twins can be partitioned into variation due to within-person environmental effects and between-person genetic effects.
Project description:Gene expression studies were performed to identify pathways possibly dysregulated by mutant in the gene GM-NM-1(olf). These experiments employed RNA derived from lymphoblastoid cell lines established for 4 affected carriers and 4 non-carriers. In comparison to endogenous control and other dystonia-associated genes, GNAL was expressed at relatively low levels in lymphoblastoid cell lines. Comparison of whole blood expression profiles of mutation carrying dystonia patients with normal controls
Project description:The degree to which the level of genetic variation for gene expression is shared across multiple tissues has important implications for research investigating the role of expression on the aetiology of complex human traits and diseases. In the last few years, a number of studies have been published reporting the extent of overlap in expression quantitative trait loci (eQTL) identified in multiple tissues or cell types. Whilst these studies provide important information on the regulatory control of genes across tissues, their limited power means they can typically only explain a small proportion of genetic variation for gene expression. Here, using expression data from monozygotic twins (MZ), we investigate the genetic control of gene expression in lymphoblastoid cell lines (LCL) and whole blood (WB). We estimate the genetic correlation which represents the combined effects of all causal loci across the whole genome and is a measure of the level of common genetic control of gene expression between the two RNA sources. Our results show that, when averaged across the genome, mean levels of genetic correlation for gene expression in LCL and WB samples are close to zero. We support our results with evidence from gene expression in an independent sample of LCL, T-cells and Fibroblasts. In addition, we provide evidence that housekeeping genes, which maintain basic cellular functions, are more likely to have high genetic correlations between the RNA sources than non-housekeeping gene, implying a relationship between the transcript function and the degree to which a gene has tissue specific genetic regulatory control.
Project description:Autism spectrum disorders (ASDs) are relatively common neurodevelopmental conditions whose biological basis has been incompletely determined. We analyzed the metabolic profile of lymphoblastoid cell lines from patients with ASDs and normal individuals, using the Biolog Phenotype plates. To validate our metabolic findings, we utilized the Agilent Whole Human Genome Oligo Microarray to evaluate the level of gene expression in the tested cell lines. As a comparison for gene expression profiles in cells of patients with ASDs, we also performed microarray analysis for lymphoblastoid cell lines from patients with intellectual disability (ID). Two independent experiments were performed for each sample. To maximize the contrast between samples, we implemented a loop experimental design.
Project description:Homo sapiens fresh whole blood was infected with Candida parapsilosis. RNA-pool of both species extracted at 0min (control), 15, 30, 60, 120, 240 min. Samples are rRNA depleted. Measurement of Homo sapiens gene expression.