Gene expression levels can vary across individuals in the general population and between monozygotic twins. Both genetic and nongenetic factors are assumed to contribute to the variable expression. However, little evidence supporting this notion has been obtained from empirical data. Here, we used the expression data from a large twin cohort to dissect genetic and nongenetic effects on the formation of expression variability QTLs (evQTLs)—i.e., genetic loci associated with or linked to variants that influence the variance of gene expression. Our findings have implications for understanding divergent sources of gene expression variability.
Human mitochondria contain multiple copies of a circular genome made up of double-stranded DNA (mtDNA) that encodes proteins involved in cellular respiration. Transcript abundance of mtDNA-encoded genes varies between human individuals, yet the level of variation in the general population has not been systematically assessed. In the present study, we revisited large-scale RNA sequencing data generated from lymphoblastoid cell lines of HapMap samples of European and African ancestry to estimate transcript abundance and quantify expression variation for mtDNA-encoded genes. In both populations, we detected up to over 100-fold difference in mtDNA gene expression between individuals. The marked variation was not due to differences in mtDNA copy number between individuals, but was shaped by the transcription of hundreds of nuclear genes. Many of these nuclear genes were co-expressed with one another, resulting in a module-enriched co-expression network. Significant correlations in expression between genes of the mtDNA and nuclear genomes were used to identify factors involved with the regulation of mitochondrial functions. In conclusion, we determined the baseline amount of variability in mtDNA gene expression in general human populations and catalogued a complete set of nuclear genes whose expression levels are correlated with those of mtDNA-encoded genes. Our findings will enable the integration of information from both mtDNA and nuclear genetic systems, and facilitate the discovery of novel regulatory pathways involving mitochondrial functions.
is a significant opportunistic fungal pathogen in Southeast Asia. This species is unique in that it is the only dimorphic member of the genus. It undergoes multicellular hyphal growth and asexual development (conidiation) in the environment at 25°C and unicellular yeast growth in macrophages at 37°C. Both the thermal dimorphism and the ability to survive inside host macrophages are important for P. marneffei
to establish infection. We employ genomic and transcriptomic methodologies to study the molecular basis for the temperature-dependent dimorphic switching program in P. marneffei
PM1. The information generated from this study provides the foundation for future work directed at characterizing the underlying mechanisms of cellular development in this fungus. [Read on...
Ishita Mandhan who is working on a project evaluating the impact of loss-of-function mutations on gene transcription receives the ECEN Undergraduate Research Award. The purpose of this one-time scholarship is to encourage and support research for undergraduate students. Donor representative of the program is Dr. Chanan Singh, Regents Professor, Irma Runyon Chair Professor at the Electrical and Computer Engineering Department, TAMU.
The 1000 genomes toxicity screening project is led by Prof. Ivan Rusyn
. The goals of this project are to (i) develop toxicogenetic expression quantitative trait loci (eQTL) mapping tools, perform transcription factor network inference and integrative pathway assessment; (ii) perform toxicogenetic modeling of liver toxicity in cultured mouse hepatocytes; (iii) discover chemical-induced regulatory networks using population-based toxicity phenotyping in human cells. For details, see
NIEHS-NCATS-UNC DREAM Toxicogenetics Challenge (syn1761567
Gang is selected to receive a George Bush Presidential Library Foundation Travel Grant. The intent of this award is to provide educational opportunities to Texas A&M students in support of travel to conferences, research projects study, or interships in the US or abroad. Gang is selected by CVM college because of his exemplary academic record and the opportunity for travel in pursuit of his educational objectives. Gang will be using this award to attend SMBE 2013
Increasing evidence suggests that the variance (as opposed to the mean) among phenotypes may be genotype-dependent. Conventional eQTL analysis focuses on the mean, instead of the variance, of gene expression. In a paper published in Genetics
, Amanda Hulse and James Cai perform an analysis that identifies what we describe as evQTL—loci associated with the variances of gene expression among three possible genotypes of a biallelic SNP. The discovered evQTL provide orthogonal information, unavailable in existing eQTL literature, on genetic control of gene expression. The evQTL can act in single-SNP and multiple-SNP effects. Detecting evQTL may represent a novel method for effectively screening for genetic interactions. [Read on...
Genes within the major histocompatibility complex (MHC) encode proteins involved in innate and adaptive immune responses. Genetic variation in this region can influence the immune response of an individual animal to challenges from a variety of pathogens; however, a complete documentation of genetic variation in the MHC is lacking for most domestic animals, including horses. To provide additional genetic markers for study of the horse MHC, or ELA (equine lymphocyte antigen), we identified 37 polymorphic microsatellite repeats in ELA and used these variations separately and together with published SNPs to investigate linkage disequilibrium (LD) and haplotype structure in a sample of Thoroughbred horses. ELA SNPs alone detected little LD, but microsatellites, either separately or combined with SNPs, revealed substantially more LD. A subset of markers in very high LD across the breadth of ELA may be predictive of structural polymorphisms or linked epistases that are important drivers of haplotype structure in Thoroughbreds. [PubMed
Ishita Mandhan is an undergraduate student of the Departments of Electrical & Computer Engineering
, TAMU. She is interested in application of computational approaches in processing large-scale genomics data. Thanks to the Undergraduate Research Scholars Program. Her scholars application has been accepted on Sep. 27, 2012. Congratulations and welcome to the 2012-13 class of Undergraduate Research Scholars! She will be participating Scholars Orientation and Welcome Bar B Q on October 10th in the Interdisciplinary Life Sciences Building. After the kick-off, Ishita will start working on a population-level evaluation of the impact of loss-of-function mutations and GWAS mutations on human transcriptomes.
We present SBEToolbox (Systems Biology and Evolution Toolbox), an open-source Matlab toolbox for biological network analysis. It takes a network file as input, calculates a variety of centralities and topological metrics, clusters nodes into modules, and interactively displays the network using different graph layout algorithms. Efficient lightweight design allows large-scale networks to be handled. Straightforward implementation and the inclusion of high-level functions allow the functionality to be easily extended or tailored. SBEGUI, a menu-driven Graphical User Interface (GUI) of SBEToolbox, is highly interactive, enabling easy usage of most network and graph algorithms without prior knowledge of programming. The stand-alone executable SBEGUI, running on all major operating systems, does not require the installation of Matlab system. Availability: Pre-compiled stand-alone executable for all major operating systems and source code are freely available at http://sbetoolbox.sourceforge.net