NIH Completes Atlas Detailing Human DNA

Researchers funded by the National Institutes of Health, completed a detailed atlas documenting human DNA which influence gene expression.

The atlas, a key way a person’s genome identifies an observable trait, is a critical resource for the scientific community interested in how individual genomic variation leads to biological differences.

The Genotype-Tissue Expression (GTEx) Consortium culminated to establish a catalog on how genomic variation influences the power of genes to turn on or off. There was no prior resource at scale used to study how gene expression in 1 part of the body may differ from another, and how those differences relate to the inherited genomic variation that make up an individual.

Research was collected from more than 53 different tissue types in the brain, liver and lung, from autopsy, organ donations and tissue transplant programs in 960 donors.

The data will help researchers understand the mechanisms of how genes are expressed in a variety of tissues, improving knowledge of how genes are mis-regulated in the context of disease. Data can also be used to understand the variations of gene expression among healthy individuals.

Data currently available to the public through the GTEx Portal is designed for storing, cataloging, searching and sharing aggregated level data and raw data found in the Database of Genotypes and Phenotypes (dbGaP) — developed to archive and distribute data and results from various studies investigating the interaction of genotype and phenotype in humans.

The project, which was launched in 2010 and concluded summer 2017, houses a biobank of collected tissue samples and extracted DNA and RNA to use in future studies by independent researchers.

The overall aim of GTEx was to create a public atlas of human DNA, allowing researchers to analyze the effect of genetic variation and gene expression, aiding the functional interpretation of disease genetics.

The data can also provide use in other functional genomic patterns to potentially identify variation influencing like alterative splicing, the use of alternative transcription start sites, RNA editing and X chromosome inactivation.

The project was supported by the NIH Common Fund and administered by functional arms of the NIH: NHGRI, NIMH and the National Cancer Institute (NCI).

GTEx data was used in a recent study published in Nature, which focused on expression quantitative trait locus (eQTL) mapping in 44 different human tissues from 449 individuals.

RNA was extracted and sequenced to ascertain the expression levels of genes in each tissue and data was tallied against each donor’s genotype.

The study found that local genetic variation affects gene expression levels for the majority of genes. In addition to identifying the locally acting variants, the project revealed that for certain genes, variants on other chromosomes could be associated with expression levels. Many of the expression-associated genetic variants overlap with genetic loci previously found associated with disease. Researchers were able to identify inter-chromosomal genetic effects for 93 genes and 112 loci.

A project known as Enhancing GTEx (eGTEx), which started in 2013, extends the effort to combine gene expression studies with additional measurements like protein expression. It’s being conducted on the same tissues used in the GTEx project, which provides a greater resource integrating the complexity of genomes functioning in biologically significant ways.

A press release was made available.