A more personal view of human-gene regulation

A more personal view of human-gene regulation

A long-planned effort to examine gene expression and gene regulation in all the major tissues in the human body across many people comes to fruition.

11 October 2017

(http://www.nature.com/news/a-more-personal-view-of-human-gene-regulation-1.22794)

Hundreds of post-mortem tissue samples have been analysed for gene expression.

“The observation of and the search for similarities and differences are the basis of all human knowledge,” Alfred Nobel once said. From external events to spiritual influence, each culture and time has found its own way to explain how we differ from each other and what we have in common. Today, much biological effort focuses on the similarities and differences between people’s DNA, and probing the myriad ways that these can combine, for good or ill, is at the cutting edge of genetics.

This week, geneticists announce the results of one such project. The researchers describe how they have analysed the regulatory code in our genomes. This should help scientists to unpick how genetic variants associated with disease function in different tissues of the body.

The project is called GTEx (genotype-tissue expression) and it catalogues genetic variation and its influence on gene expression in 44 tissues across the human body. The results — published in four papers (see pages 204, 239, 244 and 249) and discussed in an accompanying News and Views article — show how most of these critical regulatory regions are located close to the gene they affect. And they report important differences in gene regulation between tissues and between individuals. These results build on the findings of a pilot study that were announced in 2015.

The project results were a long time coming and were widely anticipated. The GTEx study was first proposed back in 2008. Its goal was to establish a resource database and an associated biobank (holding all major human tissues from 1,000 deceased individuals) that could be used by scientists to study the relationship between genetic variation and gene expression.

That seemed so far beyond technical capabilities at the time that many dismissed the idea as unrealistic. How could that many tissues be sampled from a single donor? How could so many individuals be recruited and be appropriately consented? How could high-quality samples be taken within the required post-mortem interval (different for various tissues)? And would the data even reflect living biology and replicate known findings on gene regulation?

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