Roderic Guigó: “We look for differences in gene expression between both tissues and individuals”

The international Genotype-Tissue Expression project (GTEx) began in 2010 with the aim of creating a database and tissue bank that would allow scientists to study the relationship between genetic variation and gene expression in human tissues. On April 20 and 21 a meeting will be held at the PRBB for this project, which is financed with more than $15 million, mainly from the National Institutes of Health (NIH). Researchers from nine countries are taking part in the project, including a CRG team led by Roderic Guigó.

What does the GTEx project consists of?

The main objective of the project is to determine differences in gene expression depending on which tissues they belong to. Samples have been obtained from around 900 volunteers who donated their bodies after death. Between 20 and 30 tissues and organs have been taken, for which we have sequenced the DNA (the genome) and the RNA (the genome expression). The donors are aged from 21 to 70 and ideally have no pathologies, as we want to define normal gene expression.

We also study the variation in gene expression between individuals to see whether differences in expression correlate with phenotypic characteristics such as sex, age, height, weight, and also with drug use or the cause of death. For example, every cell in my body has the same DNA, but my skin cells are not the same as my brain cells because the RNA is expressed differently. Moreover, the RNA expressed in my skin is different from that expressed in the skin of another person. Because of this we study both dimensions: differences between tissues and between individuals.

What challenges does the project face?

To understand the tissue transcriptome at a molecular level, unfortunately we have to get samples from a deceased person. So the biggest challenge is getting the samples. Usually when a person dies and some of their organs are donated for transplants, their relatives are asked if they will give the others to this project.

Moreover, organs must be extracted very quickly, at most 24 hours after death, because they deteriorate. Throughout the project this process has been highly optimised and is now carried out within four or five hours. Without all the logistical organisation this project would have been impossible – it is what makes it unique. Another major challenge is analysing the large volume of data because we have 20-30 thousand samples which have each been sequenced for RNA and studied for gene expression at all levels.

Most transcriptional changes occur during growth, possibly before the age of 21. For this reason, one limitation of the project is the fact that certain ages are poorly represented because, thankfully, young people die less.

What do you think the next steps in the project should be?

On the one hand, we have a very small and biased representation of the human population, as all individuals are from a particular region in the United States. In the future it would be interesting to recruit individuals of other ethnicities. Organs and tissues are very complex structures, and we have samples of globally-extracted RNA, whereas we would now like to study tissue sub-regions in a more specific way.

This Interview by Mari Carmen Cebrián was published in El·lipse #103

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