The Common Fund's Genotype-Tissue Expression (GTEx) Program established a data resource and tissue bank to study the relationship between genetic variation and gene expression in multiple human tissues. GTEx is also examining sex-based differences in how genes are turned on and off and how they are regulated. GTEx resources are valuable tools for exploring the genetic basis of complex human diseases.
The GTEx program started in 2010, and the GTEx portal that provides access to GTEx resources was launched in 2013. The GTEx data resource consists of whole-genome sequence and RNA-sequence from ~650 deceased adult donors, with multiple tissue samples collected per donor (e.g. lung, brain, pancreas, skin, etc.). The data resource stimulated research on the genetic basis of complex diseases. By 2017, over 650 papers were published using data from the GTEx data resource. In November 2017, GTEx investigators published a series of manuscripts in Nature on developing novel methods to study the mechanisms of gene regulation.
The GTEx Program supported 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
GTEx collected multiple human tissues (i.e. brain, heart, lung, breast, skin and whole blood etc.) from ~960 donors and over 30,000 samples.These tissues and samples are stored through the National Cancer Institute's Cancer Human Biobank initiative on behalf of GTEx. The GTEx database is available to researchers through the GTEx Portal. GTEx is helping researchers understand the inherited susceptibility to common diseases such as cancer, heart disease, Parkinson’s and diabetes.
GTEx also included a study to understand the ethical, legal and social issues (ELSI) related to donor recruitment and consent to tissue donation for biobanking purposes. In 2017, the GTEx ELSI researchers published a paper in Genetic Testing and Molecular Biomarkers. The findings indicated that a clear discussion about risks and benefits associated with participation in biobanking research is needed during the consent process.
Correlations between genotype and tissue-specific gene expression levels
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.
This page last reviewed on May 18, 2018