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Program Snapshot

The Common Fund's Genotype-Tissue Expression (GTEx) program is providing valuable insights into the mechanisms of gene regulation by studying human gene expression and regulation in multiple tissues from health individuals; exploring disease-related perturbations in a variety of human diseases; and examining sexual dimorphisms in gene expression and regulation in multiple tissues. Genetic variation between individuals – underlying the many differences in gene expression – will be examined for correlation with differences in gene expression level to identify regions of the genome that influence whether and how much a gene is expressed. Identifying unique genomic variations associated with gene expression is expected to stimulate research towards understanding the genetic basis of complex diseases.

The GTEx project includes the following initiatives:

  • Online data resource (GTEx Portal) for storing, cataloging, searching, and sharing aggregated level data
  • Novel Statistical Methods for Human Gene Expression Quantitative Trait Loci (eQTL) Analysis
  • Laboratory, Data Analysis, and Coordinating Center (LDACC) for acquiring and analyzing DNA and RNA from multiple human tissues
  • Enhanced GTEx projects: including additional dimensions beyond gene expression to the GTEx data


Program Highlights

GTEx dataset making a splash in evolutionary genetics
Following modern humans exodus from Africa ~60,000 years ago they encountered now-extinct Neandertals and on at least a few occasions interbreeding occurred. As a result, genomes of modern Eurasians contain ~1.5 to 4% Neandertal DNA. However, the contribution(s) of this DNA to modern human’s physiology and disease susceptibility/progression is only beginning to be understood. In a recent Science publication, Simonti and coworkers identified two single nucleotide polymorphisms (SNP) within the introgressed Neandertal DNA that were associated with disease. A SNP in the intron of P-selectin (SELP) was associated with a hypercoagulable state while a second upstream of stromal interaction molecule 1 (STIM1) was associated with incontinence, bladder pain, and urinary tract disorders. Because of the GTEx dataset they were able to show that both Neandertal SNPs are associated with changes in SELP (increased) and STIM1 (decreased) gene expression, suggesting that the effects from modern human-Neandertal interbreeding are still with us today.

Read the original research article (institutional subscription may be required for full text). 

GTEx hopes to play a major role in uncovering genetic loci contributing to psychiatric disorders
Genome wide association studies (GWAS) have identified over 100 genetic loci associated with schizophrenia diagnosis. However, GWAS studies have limited ability to uncover how genetic loci associated with schizophrenia diagnosis alter biological processes resulting in risk for or protection from schizophrenia or whether those genetic loci associated with schizophrenia diagnosis are amenable to interventions. The GTEx program is optimistic that its sequence database containing over 900 post-mortem donors – over 420 of them whole brain donors – will help to untangle how the over 100 loci associated with schizophrenia diagnosis actually function in the progression of the disease. This week, a highly publicized Nature paper uncovered the biological basis for why the major histocompatibility complex locus, a GWAS-identified genetic loci spanning several megabases, is associated with schizophrenia diagnosis. With the aid of GTEx data from brain frontal cortex, the researchers showed that each common complement component 4A (C4A) allele associates with schizophrenia in proportion to its tendency to generate greater expression of C4A mRNA.

GTEx Perspective: Understanding how non-coding genomic polymorphisms affect gene expression 
Read the Nature paper
Read a Washington Post article on the Nature paper

Additional Information

You and GTEx: Updated Informational Brochure

Visit the GTEx website for Donors and Families

For any questions, please contact Casey Martin at GTEXInfo@mail.nih.gov

GTEx will hold two scientific meetings on July 11-13, 2016 at Stanford University. Day 1 (July 11th) is open to anyone within the scientific community and it will highlight current data sets and types available, various tools being developed for these data types, and results from applying them to the data. Resister and submit an abstract for Day 1 here. Abstracts due May 16, 2016. Days 2-3 (July 12th & 13th) is a closed meeting for GTEx consortium members; consortium members can register for Days 2-3 here.

GTEx Reaches Midpoint Milestone!
The GTExPortal was updated in October 2015! This latest version of sequence data encompasses roughly half of the anticipated 960 postmortem donors. This release includes genotype data from approximately 450 donors and over 9600 RNA-seq samples across 51 tissue sites and 2 cell lines, with adequate power to detect Expression Quantitative Trait Loci in 44 tissues. Full gene and isoform expression datasets are available for download through the GTEx Portal while genotypes and RNA-seq bam files are available via dbGaP.

GTEx Pilot Phase Data Show How Differences in DNA Affect Gene Activity and Disease Susceptibility. Analyses from the GTEx pilot phase were recently published in Science and other journals. Learn how the GTEx resource is poised to advance our understanding of how genetics and gene activity affect human health and disease. Read a brief summary of the potential of the GTEx resource and some of the pilot phase findings. Read the Press Release.

The Genotype-Tissue Expression Project (GTEx) Biospecimens Access Policy is a mechanism  to allow researchers access to tissues in the GTEx biobank. The policy and related forms can be found on the GTEx PortalGo directly to GTEx Sample Request Forms.


The GTEx (Genotype-Tissue Expression) Project


Correlations between genotype and tissue-specific gene expression levels will help identify regions of the genome that influence whether and how much a gene is expressed.Top: DNA and RNA is collected and analyzed from multiple tissues. Each donor has different genetic variants. In this example they are G/G, A/G, and A/A. Middle: Gene expression levels (RNA) are measured in each tissue from each individual and correlated with that individual’s genotype. Each donor has different gene expression (RNA) levels. In this example donor 1 has the highest while donor 3 has the lowest RNA levels in brain. Donor 2 is in the middle. RNA expression levels are treated as quantitative traits or expression quantitative trait loci (eQTLs). When eQTLs are correlated with genetic variation new genetic variants associated with, and potentially causal to, gene expression are discovered. In this example the genetic variant G/G is associated with high gene expression in brain while the genetic variant A/A is associated with low gene expression in brain. The genetic variant A/G is associated with intermediate gene expression in brain. When eQTLs between healthy and unhealthy individuals are compared, novel genes contributing to disease can be discovered. Bottom: The eQTL data and the donor tissues are deposited in the GTEx Portal and tissue repository for use by the scientific community.


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