11 September 2020 Vol 369, Issue 6509
Special Issue Genetic Variation
Introduction to special issue
The custom transcriptome
Laura M. Zahn
The panorama of human phenotypes arises from a mix of common and rare genetic variants, some of which affect how genes are expressed and spliced throughout the body. More than a decade ago, scientists aiming to better understand the effects of genetic diversity in healthy individuals launched the Genotype-Tissue Expression (GTEx) Consortium. Here, Science unveils the third and final phase of the project, presenting the results from the analysis of the version 8 (v8) GTEx release.
The v8 data release includes an increased number of tissues and individuals, which allows for more accurate mapping of putatively causal variants and identifies cell type–specific differences in gene expression. The increased size of the study also provides the power to link genetic variation to gene expression, both proximally and distally in the genome, so that cis and trans effects as well as population- and sex-specific differences in gene expression can be detected.
The efforts of the GTEx Consortium have led to the development of numerous tools, including Watershed, and have provided a comprehensive resource for the scientific community. The GTEx project has established a foundation to elucidate how genetic variants affect gene regulation and quantitative traits in humans. Such studies of genetic variation and tissue specificity inform on properties of the genome—including noncoding elements and the telomeres found at chromosome ends—and help us understand how gene variants influence aging and disease. This work sets the stage for future exploration into the effects of the common and rare variants that underlie the gamut of humanity.